Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2020, Vol. 14 Issue (6) : 726-745    https://doi.org/10.1007/s11684-020-0746-0
REVIEW
Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system
Xiaohui Wang1,2,3, Zhiqiang Wu3, Wei Qiu2, Ping Chen1, Xiang Xu2(), Weidong Han3()
1. College of Biotechnology, Southwest University, Chongqing 400715, China
2. State Key Laboratory of Trauma, Burn and Combined Injury, Department of Stem Cell & Regenerative Medicine, Daping Hospital and Research Institute of Surgery, Chongqing 400042, China
3. Molecular & Immunological Department, Bio-therapeutic Department, Chinese PLA General Hospital, Beijing 100853, China
 Download: PDF(1410 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

Chimeric antigen receptor (CAR) T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies. However, CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence, in addition to antigen-negative relapse and an immunosuppressive microenvironment. Various preclinical studies are exploring strategies to overcome the above challenges. Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors. In this review, we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies, especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response. We also explored the sensitizing effects of conventional treatment approaches, such as chemotherapy and radiotherapy, on CAR T cell therapy. Finally, we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.

Keywords CAR T cells      immunoregulatory molecules      endogenous immune response      solid malignancies     
Corresponding Author(s): Xiang Xu,Weidong Han   
Just Accepted Date: 21 April 2020   Online First Date: 13 August 2020    Issue Date: 24 December 2020
 Cite this article:   
Xiaohui Wang,Zhiqiang Wu,Wei Qiu, et al. Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system[J]. Front. Med., 2020, 14(6): 726-745.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-020-0746-0
https://academic.hep.com.cn/fmd/EN/Y2020/V14/I6/726
Fig.1  Strategy for engineering CAR T cells through triggering comprehensive endogenous anti-tumor immune responses. T cell costimulatory (left) and/or inhibitory (right) pathways can be targeted to enhance CAR T cell therapy in solid tumors. CAR T cells are genetically engineered to express/secrete cytokines and/or chemokines, such as IL-18, IL-15, IL-12, IL-7, chemokine (C–C motif) ligand 19 (CCL19), and tumor necrosis factor superfamily (TNFSF) members. CAR T cells coordinate with inhibitory signals, including immune checkpoints (PD-1/PD-L1) and transforming growth factor β (TGF-β), to boost immune responses.
Fig.2  CAR T cells engineered to co-express/release immune-stimulatory molecules or block immune-inhibitory molecules indirectly mobilize the endogenous immune response by enhancing the activation and recruitment of immune cells, such as M1 macrophages, natural killer (NK) cells, T cells, and dendritic cells (DCs), and by overcoming the inhibitory microenvironment.
Module Antigen Phase Clinical trial ID Disease condition Status Sponsor
IL-12 MUC16ecto I NCT02498912 Serous ovarian, PPC, FTC Recruiting Memorial Sloan Kettering Cancer Center
IL-12 EGFR I NCT03542799 Metastatic colorectal cancer Not yet recruiting Shenzhen Second People’s Hospital
IL-7 and CCL19 or IL-12 Nectin4 I NCT03932565 NSCLC, breast cancer, ovarian cancer, bladder cancer, pancreatic cancer Recruiting The Sixth Affiliated Hospital of Wenzhou Medical University
IL-15 GD2 I NCT03721068 Relapsed/refractory neuroblastoma Recruiting UNC Lineberger Comprehensive Cancer Center
IL-15 GD2 I NCT03294954 Children with neuroblastoma Recruiting Baylor College of Medicine
IL-15 CD19 I/II NCT03579927 MCL, recurrent/refractory DLBCL, recurrent/refractory FL, refractory B cell NHL Not yet recruiting M.D. Anderson Cancer Center
IL-15 CD19 I NCT03774654 Refractory B cell NHL, refractory B cell SLL, relapsed adult ALL, relapsed CLL, relapsed NHL Not yet recruiting Baylor College of Medicine
IL-7/IL-15 CD19 I/II NCT02652910 Recurrent adult DLCL, recurrent FL, recurrent MCL, stage III/IV adult DLCL, stage III/IV FL, stage III/IV MCL Recruiting Xinqiao Hospital of Chongqing
IL-15 CD19 I/II NCT03056339 B-lymphoid malignancies, ALL, CLL, NHL Recruiting M.D. Anderson Cancer Center
IL-7 and CCL19 CD19 II NCT03929107 B cell lymphoma Recruiting Wenbin Qian
CCR4 CD30 I NCT03602157 Lymphoma, NHL, immune system diseases, immunoproliferative disorders, lymphatic diseases, lympho proliferative disorders, neoplasms, cutaneous lymphoma, cutaneous ALCL, MF, SS, lymphomatoid papulosis Recruiting UNC Lineberger Comprehensive Cancer Center
Tab.1  Summary of ongoing clinical trials investigating the combination of CAR T cells with cytokines and chemokines in cancer immunotherapy
Module Antigen Phase Clinical trial ID Disease condition Status Sponsor
Expressing PD-1 antibody EGFR family I/II NCT02873390 Advanced malignancies Unknown Ningbo Cancer Hospital
Expressing PD-1 antibody EGFR family I/II NCT02862028 Advanced solid tumor (lung, liver, and stomach) Unknown Shanghai International Medical Center
Cytoplasmic activated PD-1 CD19 I NCT03540303 Refractory/relapsed B cell lymphoma Recruiting Henan Cancer Hospital
PD-1 knockout MUC1 I/II NCT03525782 Lung cancer, NSCLC Recruiting The First Affiliated Hospital of Guangdong Pharmaceutical University
Expressing PD-1 antibody Mesothelin I/II NCT03030001 Solid tumor, adult advanced cancer Unknown Ningbo Cancer Hospital
PD-1 knockout MUC1 I/II NCT03706326 Esophageal cancer Recruiting The First Affiliated Hospital of Guangdong Pharmaceutical University
PD-1 and TCR knocked out Mesothelin I NCT03545815 Solid tumor Recruiting Chinese PLA General Hospital
PD-1 knockout CD19 I NCT03298828 ALL, Burkitt lymphoma Not yet recruiting Third Military Medical University
Expressing CTLA-4 and PD-1 antibodies EGFR I/II NCT03182816 Advanced solid tumor Unknown Shanghai Cell Therapy Research Institute
Expressing CTLA-4 and PD-1 antibodies MUC1 I/II NCT03179007 Advanced solid tumor Unknown Shanghai Cell Therapy Research Institute
Expressing CTLA-4 and PD-1 antibodies Mesothelin I/II NCT03182803 Advanced solid tumor Unknown Shanghai Cell Therapy Research Institute
PD-1 knockout Mesothelin I NCT03747965 Solid tumor Recruiting Chinese PLA General Hospital
Transduced with a PD-1/CD28 chimera lentiviral vector CD19 I NCT03932955 Lymphoma Recruiting Peking University
Combination with anti-PD-1 antibody (Pembrolizumab) CD19 and CD22 I/II NCT03287817 DLBCL, relapsed or refractory DLBCL Recruiting Autolus Limited
Expressing PD-1 antibody Mesothelin I/II NCT03615313 Advanced solid tumor Recruiting Shanghai Cell Therapy Research Institute
Combination with anti-PD-1 antibody (Pembrolizumab) EGFRvIII I NCT03726515 Glioblastoma Recruiting University of Pennsylvania
Incorporation of a PD-1shRNA expressing cassette CD19 I NCT03208556 Relapsed or refractory B cell lymphoma Recruiting Peking University
Tab.2  Summary of ongoing clinical trials investigating the combination of CAR T cells with immune checkpoint blockade in cancer immunotherapy
Module Antigen Phase Clinical trial ID Disease condition Status Sponsor
Oncolytic adenovirus HER2 I NCT03740256 Bladder cancer, HNSCC, salivary gland cancer, lung cancer, breast cancer, gastric cancer, ESCA, colorectal cancer, pancreatic adenocarcinoma Not yet recruiting Baylor College of Medicine
Tab.3  Summary of ongoing clinical trials investigating the combination of CART cells with OVs in cancer immunotherapy
1 C Zhang, J Liu, JF Zhong, X Zhang. Engineering CAR-T cells. Biomark Res 2017; 5(1): 22
https://doi.org/10.1186/s40364-017-0102-y pmid: 28652918
2 JN Brudno, JN Kochenderfer. Chimeric antigen receptor T-cell therapies for lymphoma. Nat Rev Clin Oncol 2018; 15(1): 31–46
https://doi.org/10.1038/nrclinonc.2017.128 pmid: 28857075
3 G Ding, H Chen. Adoptive transfer of T cells transduced with a chimeric antigen receptor to treat relapsed or refractory acute leukemia: efficacy and feasibility of immunotherapy approaches. Sci China Life Sci 2016; 59(7): 673–677
https://doi.org/10.1007/s11427-016-0017-3 pmid: 27142351
4 L Mikkilineni, JN Kochenderfer. Chimeric antigen receptor T-cell therapies for multiple myeloma. Blood 2017; 130(24): 2594–2602
https://doi.org/10.1182/blood-2017-06-793869 pmid: 28928126
5 G Wei, L Ding, J Wang, Y Hu, H Huang. Advances of CD19-directed chimeric antigen receptor-modified T cells in refractory/relapsed acute lymphoblastic leukemia. Exp Hematol Oncol 2017; 6(1): 10
https://doi.org/10.1186/s40164-017-0070-9 pmid: 28413717
6 S Yu, A Li, Q Liu, T Li, X Yuan, X Han, K Wu. Chimeric antigen receptor T cells: a novel therapy for solid tumors. J Hematol Oncol 2017; 10(1): 78
https://doi.org/10.1186/s13045-017-0444-9 pmid: 28356156
7 SL Maude, TW Laetsch, J Buechner, S Rives, M Boyer, H Bittencourt, P Bader, MR Verneris, HE Stefanski, GD Myers, M Qayed, B De Moerloose, H Hiramatsu, K Schlis, KL Davis, PL Martin, ER Nemecek, GA Yanik, C Peters, A Baruchel, N Boissel, F Mechinaud, A Balduzzi, J Krueger, CH June, BL Levine, P Wood, T Taran, M Leung, KT Mueller, Y Zhang, K Sen, D Lebwohl, MA Pulsipher, SA Grupp. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med 2018; 378(5): 439–448
https://doi.org/10.1056/NEJMoa1709866 pmid: 29385370
8 SJ Schuster, MR Bishop, CS Tam, EK Waller, P Borchmann, JP McGuirk, U Jäger, S Jaglowski, C Andreadis, JR Westin, I Fleury, V Bachanova, SR Foley, PJ Ho, S Mielke, JM Magenau, H Holte, S Pantano, LB Pacaud, R Awasthi, J Chu, Ö Anak, G Salles, RT Maziarz; JULIET Investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 2019; 380(1): 45–56
https://doi.org/10.1056/NEJMoa1804980 pmid: 30501490
9 SS Neelapu, FL Locke, NL Bartlett, LJ Lekakis, DB Miklos, CA Jacobson, I Braunschweig, OO Oluwole, T Siddiqi, Y Lin, JM Timmerman, PJ Stiff, JW Friedberg, IW Flinn, A Goy, BT Hill, MR Smith, A Deol, U Farooq, P McSweeney, J Munoz, I Avivi, JE Castro, JR Westin, JC Chavez, A Ghobadi, KV Komanduri, R Levy, ED Jacobsen, TE Witzig, P Reagan, A Bot, J Rossi, L Navale, Y Jiang, J Aycock, M Elias, D Chang, J Wiezorek, WY Go. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 2017; 377(26): 2531–2544
https://doi.org/10.1056/NEJMoa1707447 pmid: 29226797
10 E Zah, MY Lin, A Silva-Benedict, MC Jensen, YY Chen. T cells expressing CD19/CD20 bispecific chimeric antigen receptors prevent antigen escape by malignant B cells. Cancer Immunol Res 2016; 4(6): 498–508
https://doi.org/10.1158/2326-6066.CIR-15-0231 pmid: 27059623
11 Z Grada, M Hegde, T Byrd, DR Shaffer, A Ghazi, VS Brawley, A Corder, K Schönfeld, J Koch, G Dotti, HE Heslop, S Gottschalk, WS Wels, ML Baker, N Ahmed. TanCAR: a novel bispecific chimeric antigen receptor for cancer immunotherapy. Mol Ther Nucleic Acids 2013; 2: e105
https://doi.org/10.1038/mtna.2013.32 pmid: 23839099
12 M Ruella, DM Barrett, SS Kenderian, O Shestova, TJ Hofmann, J Perazzelli, M Klichinsky, V Aikawa, F Nazimuddin, M Kozlowski, J Scholler, SF Lacey, JJ Melenhorst, JJ Morrissette, DA Christian, CA Hunter, M Kalos, DL Porter, CH June, SA Grupp, S Gill. Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. J Clin Invest 2016; 126(10): 3814–3826
https://doi.org/10.1172/JCI87366 pmid: 27571406
13 K Bielamowicz, K Fousek, TT Byrd, H Samaha, M Mukherjee, N Aware, MF Wu, JS Orange, P Sumazin, TK Man, SK Joseph, M Hegde, N Ahmed. Trivalent CAR T cells overcome interpatient antigenic variability in glioblastoma. Neuro-oncol 2018; 20(4): 506–518
https://doi.org/10.1093/neuonc/nox182 pmid: 29016929
14 KC Straathof, MA Pulè, P Yotnda, G Dotti, EF Vanin, MK Brenner, HE Heslop, DM Spencer, CM Rooney. An inducible caspase 9 safety switch for T-cell therapy. Blood 2005; 105(11): 4247–4254
https://doi.org/10.1182/blood-2004-11-4564 pmid: 15728125
15 A Di Stasi, SK Tey, G Dotti, Y Fujita, A Kennedy-Nasser, C Martinez, K Straathof, E Liu, AG Durett, B Grilley, H Liu, CR Cruz, B Savoldo, AP Gee, J Schindler, RA Krance, HE Heslop, DM Spencer, CM Rooney, MK Brenner. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med 2011; 365(18): 1673–1683
https://doi.org/10.1056/NEJMoa1106152 pmid: 22047558
16 X Zhou, MK Brenner. Improving the safety of T-cell therapies using an inducible caspase-9 gene. Exp Hematol 2016; 44(11): 1013–1019
https://doi.org/10.1016/j.exphem.2016.07.011 pmid: 27473568
17 I Diaconu, B Ballard, M Zhang, Y Chen, J West, G Dotti, B Savoldo. Inducible caspase-9 selectively modulates the toxicities of CD19-specific chimeric antigen receptor-modified T cells. Mol Ther 2017; 25(3): 580–592
https://doi.org/10.1016/j.ymthe.2017.01.011 pmid: 28187946
18 SS Kenderian, M Ruella, O Shestova, M Klichinsky, V Aikawa, JJ Morrissette, J Scholler, D Song, DL Porter, M Carroll, CH June, S Gill. CD33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia. Leukemia 2015; 29(8): 1637–1647
https://doi.org/10.1038/leu.2015.52 pmid: 25721896
19 GL Beatty, AR Haas, MV Maus, DA Torigian, MC Soulen, G Plesa, A Chew, Y Zhao, BL Levine, SM Albelda, M Kalos, CH June. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res 2014; 2(2): 112–120
https://doi.org/10.1158/2326-6066.CIR-13-0170 pmid: 24579088
20 SC Katz, RA Burga, E McCormack, LJ Wang, W Mooring, GR Point, PD Khare, M Thorn, Q Ma, BF Stainken, EO Assanah, R Davies, NJ Espat, RP Junghans. Phase I hepatic immunotherapy for metastases study of intra-arterial chimeric antigen receptor-modified T-cell therapy for CEA+ liver metastases. Clin Cancer Res 2015; 21(14): 3149–3159
https://doi.org/10.1158/1078-0432.CCR-14-1421 pmid: 25850950
21 J Tchou, Y Zhao, BL Levine, PJ Zhang, MM Davis, JJ Melenhorst, I Kulikovskaya, AL Brennan, X Liu, SF Lacey, AD Posey Jr, AD Williams, A So, JR Conejo-Garcia, G Plesa, RM Young, S McGettigan, J Campbell, RH Pierce, JM Matro, AM DeMichele, AS Clark, LJ Cooper, LM Schuchter, RH Vonderheide, CH June. Safety and efficacy of intratumoral injections of chimeric antigen receptor (CAR) T cells in metastatic breast cancer. Cancer Immunol Res 2017; 5(12): 1152–1161
https://doi.org/10.1158/2326-6066.CIR-17-0189 pmid: 29109077
22 MC van Schalkwyk, SE Papa, JP Jeannon, T Guerrero Urbano, JF Spicer, J Maher. Design of a phase I clinical trial to evaluate intratumoral delivery of ErbB-targeted chimeric antigen receptor T-cells in locally advanced or recurrent head and neck cancer. Hum Gene Ther Clin Dev 2013; 24(3): 134–142
https://doi.org/10.1089/humc.2013.144 pmid: 24099518
23 H Harlin, Y Meng, AC Peterson, Y Zha, M Tretiakova, C Slingluff, M McKee, TF Gajewski. Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. Cancer Res 2009; 69(7): 3077–3085
https://doi.org/10.1158/0008-5472.CAN-08-2281 pmid: 19293190
24 L Cherkassky, A Morello, J Villena-Vargas, Y Feng, DS Dimitrov, DR Jones, M Sadelain, PS Adusumilli. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J Clin Invest 2016; 126(8): 3130–3144
https://doi.org/10.1172/JCI83092 pmid: 27454297
25 TF Gajewski, Y Meng, C Blank, I Brown, A Kacha, J Kline, H Harlin. Immune resistance orchestrated by the tumor microenvironment. Immunol Rev 2006; 213(1): 131–145
https://doi.org/10.1111/j.1600-065X.2006.00442.x pmid: 16972901
26 MH Kershaw, C Devaud, LB John, JA Westwood, PK Darcy. Enhancing immunotherapy using chemotherapy and radiation to modify the tumor microenvironment. OncoImmunology 2013; 2(9): e25962
https://doi.org/10.4161/onci.25962 pmid: 24327938
27 SJ Turley, V Cremasco, JL Astarita. Immunological hallmarks of stromal cells in the tumour microenvironment. Nat Rev Immunol 2015; 15(11): 669–682
https://doi.org/10.1038/nri3902 pmid: 26471778
28 GT Motz, SP Santoro, LP Wang, T Garrabrant, RR Lastra, IS Hagemann, P Lal, MD Feldman, F Benencia, G Coukos. Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors. Nat Med 2014; 20(6): 607–615
https://doi.org/10.1038/nm.3541 pmid: 24793239
29 L Labanieh, RG Majzner, CL Mackall. Programming CAR-T cells to kill cancer. Nat Biomed Eng 2018; 2(6): 377–391
https://doi.org/10.1038/s41551-018-0235-9 pmid: 31011197
30 JP Leonard, ML Sherman, GL Fisher, LJ Buchanan, G Larsen, MB Atkins, JA Sosman, JP Dutcher, NJ Vogelzang, JL Ryan. Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-γ production. Blood 1997; 90(7): 2541–2548
pmid: 9326219
31 D Chinnasamy, Z Yu, SP Kerkar, L Zhang, RA Morgan, NP Restifo, SA Rosenberg. Local delivery of interleukin-12 using T cells targeting VEGF receptor-2 eradicates multiple vascularized tumors in mice. Clin Cancer Res 2012; 18(6): 1672–1683
https://doi.org/10.1158/1078-0432.CCR-11-3050 pmid: 22291136
32 HJ Pegram, TJ Purdon, DG van Leeuwen, KJ Curran, SA Giralt, JN Barker, RJ Brentjens. IL-12-secreting CD19-targeted cord blood-derived T cells for the immunotherapy of B-cell acute lymphoblastic leukemia. Leukemia 2015; 29(2): 415–422
https://doi.org/10.1038/leu.2014.215 pmid: 25005243
33 V Hoyos, B Savoldo, C Quintarelli, A Mahendravada, M Zhang, J Vera, HE Heslop, CM Rooney, MK Brenner, G Dotti. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia 2010; 24(6): 1160–1170
https://doi.org/10.1038/leu.2010.75 pmid: 20428207
34 M Chmielewski, H Abken. CAR T cells releasing IL-18 convert to T-Bethigh FoxO1low effectors that exhibit augmented activity against advanced solid tumors. Cell Reports 2017; 21(11): 3205–3219
https://doi.org/10.1016/j.celrep.2017.11.063 pmid: 29241547
35 H Tang, Y Wang, LK Chlewicki, Y Zhang, J Guo, W Liang, J Wang, X Wang, YX Fu. Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade. Cancer Cell 2016; 29(3): 285–296
https://doi.org/10.1016/j.ccell.2016.02.004 pmid: 26977880
36 L Zhang, SP Kerkar, Z Yu, Z Zheng, S Yang, NP Restifo, SA Rosenberg, RA Morgan. Improving adoptive T cell therapy by targeting and controlling IL-12 expression to the tumor environment. Mol Ther 2011; 19(4): 751–759
https://doi.org/10.1038/mt.2010.313 pmid: 21285960
37 MP Colombo, G Trinchieri. Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev 2002; 13(2): 155–168
https://doi.org/10.1016/S1359-6101(01)00032-6 pmid: 11900991
38 HJ Wagner, CM Bollard, S Vigouroux, MH Huls, R Anderson, HG Prentice, MK Brenner, HE Heslop, CM Rooney. A strategy for treatment of Epstein–arr virus-positive Hodgkin’s disease by targeting interleukin 12 to the tumor environment using tumor antigen-specific T cells. Cancer Gene Ther 2004; 11(2): 81–91
https://doi.org/10.1038/sj.cgt.7700664 pmid: 14685154
39 HJ Pegram, JC Lee, EG Hayman, GH Imperato, TF Tedder, M Sadelain, RJ Brentjens. Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning. Blood 2012; 119(18): 4133–4141
https://doi.org/10.1182/blood-2011-12-400044 pmid: 22354001
40 M Chmielewski, AA Hombach, H Abken. Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma. Immunol Rev 2014; 257(1): 83–90
https://doi.org/10.1111/imr.12125 pmid: 24329791
41 M Chmielewski, C Kopecky, AA Hombach, H Abken. IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression. Cancer Res 2011; 71(17): 5697–5706
https://doi.org/10.1158/0008-5472.CAN-11-0103 pmid: 21742772
42 M Koneru, TJ Purdon, D Spriggs, S Koneru, RJ Brentjens. IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors in vivo. OncoImmunology 2015; 4(3): e994446
https://doi.org/10.4161/2162402X.2014.994446 pmid: 25949921
43 M Koneru, R O’Cearbhaill, S Pendharkar, DR Spriggs, RJ Brentjens. A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16(ecto) directed chimeric antigen receptors for recurrent ovarian cancer. J Transl Med 2015; 13(1): 102
https://doi.org/10.1186/s12967-015-0460-x pmid: 25890361
44 Y Liu, S Di, B Shi, H Zhang, Y Wang, X Wu, H Luo, H Wang, Z Li, H Jiang. Armored inducible expression of IL-12 enhances antitumor activity of glypican-3-targeted chimeric antigen receptor-engineered T cells in hepatocellular carcinoma. J Immunol 2019; 203(1): 198–207
https://doi.org/10.4049/jimmunol.1800033 pmid: 31142602
45 LV Hurton, H Singh, AM Najjar, KC Switzer, T Mi, S Maiti, S Olivares, B Rabinovich, H Huls, MA Forget, V Datar, P Kebriaei, DA Lee, RE Champlin, LJ Cooper. Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells. Proc Natl Acad Sci USA 2016; 113(48): E7788–E7797
https://doi.org/10.1073/pnas.1610544113 pmid: 27849617
46 RM Teague, BD Sather, JA Sacks, MZ Huang, ML Dossett, J Morimoto, X Tan, SE Sutton, MP Cooke, C Ohlén, PD Greenberg. Interleukin-15 rescues tolerant CD8+ T cells for use in adoptive immunotherapy of established tumors. Nat Med 2006; 12(3): 335–341
https://doi.org/10.1038/nm1359 pmid: 16474399
47 J Marks-Konczalik, S Dubois, JM Losi, H Sabzevari, N Yamada, L Feigenbaum, TA Waldmann, Y Tagaya. IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice. Proc Natl Acad Sci USA 2000; 97(21): 11445–11450
https://doi.org/10.1073/pnas.200363097 pmid: 11016962
48 CA Klebanoff, SE Finkelstein, DR Surman, MK Lichtman, L Gattinoni, MR Theoret, N Grewal, PJ Spiess, PA Antony, DC Palmer, Y Tagaya, SA Rosenberg, TA Waldmann, NP Restifo. IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells. Proc Natl Acad Sci USA 2004; 101(7): 1969–1974
https://doi.org/10.1073/pnas.0307298101 pmid: 14762166
49 B Mlecnik, G Bindea, HK Angell, MS Sasso, AC Obenauf, T Fredriksen, L Lafontaine, AM Bilocq, A Kirilovsky, M Tosolini, M Waldner, A Berger, WH Fridman, A Rafii, V Valge-Archer, F Pagès, MR Speicher, J Galon. Functional network pipeline reveals genetic determinants associated with in situ lymphocyte proliferation and survival of cancer patients. Sci Transl Med 2014; 6(228): 228ra37
https://doi.org/10.1126/scitranslmed.3007240 pmid: 24648340
50 S Dadi, S Chhangawala, BM Whitlock, RA Franklin, CT Luo, SA Oh, A Toure, Y Pritykin, M Huse, CS Leslie, MO Li. Cancer immunosurveillance by tissue-resident innate lymphoid cells and innate-like T cells. Cell 2016; 164(3): 365–377
https://doi.org/10.1016/j.cell.2016.01.002 pmid: 26806130
51 MA Cheever. Twelve immunotherapy drugs that could cure cancers. Immunol Rev 2008; 222(1): 357–368
https://doi.org/10.1111/j.1600-065X.2008.00604.x pmid: 18364014
52 C Hsu, MS Hughes, Z Zheng, RB Bray, SA Rosenberg, RA Morgan. Primary human T lymphocytes engineered with a codon-optimized IL-15 gene resist cytokine withdrawal-induced apoptosis and persist long-term in the absence of exogenous cytokine. J Immunol 2005; 175(11): 7226–7234
https://doi.org/10.4049/jimmunol.175.11.7226 pmid: 16301627
53 G Krenciute, BL Prinzing, Z Yi, MF Wu, H Liu, G Dotti, IV Balyasnikova, S Gottschalk. Transgenic expression of IL15 improves antiglioma activity of IL13Ra2-CAR T cells but results in antigen loss variants. Cancer Immunol Res 2017; 5(7): 571–581
https://doi.org/10.1158/2326-6066.CIR-16-0376 pmid: 28550091
54 G Baldassarre, M Fedele, S Battista, A Vecchione, AJ Klein-Szanto, M Santoro, TA Waldmann, N Azimi, CM Croce, A Fusco. Onset of natural killer cell lymphomas in transgenic mice carrying a truncated HMGI-C gene by the chronic stimulation of the IL-2 and IL-15 pathway. Proc Natl Acad Sci USA 2001; 98(14): 7970–7975
https://doi.org/10.1073/pnas.141224998 pmid: 11427729
55 C Badoual, G Bouchaud, NH Agueznay, E Mortier, S Hans, A Gey, F Fernani, S Peyrard, PL -Puig, P Bruneval, X Sastre, A Plet, L Garrigue-Antar, F Quintin-Colonna, WH Fridman, D Brasnu, Y Jacques, E Tartour. The soluble a chain of interleukin-15 receptor: a proinflammatory molecule associated with tumor progression in head and neck cancer. Cancer Res 2008; 68(10): 3907–3914
https://doi.org/10.1158/0008-5472.CAN-07-6842 pmid: 18483276
56 Fabbi M, Ferrini S.Dual roles of IL-15 in cancer biology. J Cytokine Biol 2016; 1(2): 1000103
https://doi.org/10.4172/2576-3881.1000103
57 MJ Robertson, JM Kirkwood, TF Logan, KM Koch, S Kathman, LC Kirby, WN Bell, LM Thurmond, J Weisenbach, MM Dar. A dose-escalation study of recombinant human interleukin-18 using two different schedules of administration in patients with cancer. Clin Cancer Res 2008; 14(11): 3462–3469
https://doi.org/10.1158/1078-0432.CCR-07-4740 pmid: 18519778
58 LS Schwartzberg, I Petak, C Stewart, PK Turner, J Ashley, DM Tillman, L Douglas, M Tan, C Billups, R Mihalik, A Weir, K Tauer, S Shope, JA Houghton. Modulation of the Fas signaling pathway by IFN-γ in therapy of colon cancer: phase I trial and correlative studies of IFN-γ, 5-fluorouracil, and leucovorin. Clin Cancer Res 2002; 8(8): 2488–2498
pmid: 12171874
59 B Hu, J Ren, Y Luo, B Keith, RM Young, J Scholler, Y Zhao, CH June. Augmentation of antitumor immunity by human and mouse CAR T cells secreting IL-18. Cell Rep 2017; 20(13): 3025–3033
https://doi.org/10.1016/j.celrep.2017.09.002 pmid: 28954221
60 MP Avanzi, O Yeku, X Li, DP Wijewarnasuriya, DG van Leeuwen, K Cheung, H Park, TJ Purdon, AF Daniyan, MH Spitzer, RJ Brentjens. Engineered tumor-targeted T cells mediate enhanced anti-tumor efficacy both directly and through activation of the endogenous immune system. Cell Rep 2018; 23(7): 2130–2141
https://doi.org/10.1016/j.celrep.2018.04.051 pmid: 29768210
61 J Kwoczek, SB Riese, S Tischer, S Bak, J Lahrberg, M Oelke, H Maul, R Blasczyk, M Sauer, B Eiz-Vesper. Cord blood-derived T cells allow the generation of a more naïve tumor-reactive cytotoxic T-cell phenotype. Transfusion 2018; 58(1): 88–99
https://doi.org/10.1111/trf.14365 pmid: 29023759
62 T Shum, B Omer, H Tashiro, RL Kruse, DL Wagner, K Parikh, Z Yi, T Sauer, D Liu, R Parihar, P Castillo, H Liu, MK Brenner, LS Metelitsa, S Gottschalk, CM Rooney. Constitutive signaling from an engineered IL7 receptor promotes durable tumor elimination by tumor-redirected T cells. Cancer Discov 2017; 7(11): 1238–1247
https://doi.org/10.1158/2159-8290.CD-17-0538 pmid: 28830878
63 JC Markley, M Sadelain. IL-7 and IL-21 are superior to IL-2 and IL-15 in promoting human T cell-mediated rejection of systemic lymphoma in immunodeficient mice. Blood 2010; 115(17): 3508–3519
https://doi.org/10.1182/blood-2009-09-241398 pmid: 20190192
64 S Stoiber, BL Cadilha, MR Benmebarek, S Lesch, S Endres, S Kobold. Limitations in the design of chimeric antigen receptors for cancer therapy. Cells 2019; 8(5): E472
https://doi.org/10.3390/cells8050472 pmid: 31108883
65 OO Yeku, TJ Purdon, M Koneru, D Spriggs, RJ Brentjens. Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment. Sci Rep 2017; 7(1): 10541
https://doi.org/10.1038/s41598-017-10940-8 pmid: 28874817
66 M Martinez, EK Moon. CAR T cells for solid tumors: new strategies for finding, infiltrating, and surviving in the tumor microenvironment. Front Immunol 2019; 10: 128
https://doi.org/10.3389/fimmu.2019.00128 pmid: 30804938
67 S Mardiana, BJ Solomon, PK Darcy, PA Beavis. Supercharging adoptive T cell therapy to overcome solid tumor-induced immunosuppression. Sci Transl Med 2019; 11(495): eaaw2293
https://doi.org/10.1126/scitranslmed.aaw2293 pmid: 31167925
68 I Siddiqui, M Erreni, M van Brakel, R Debets, P Allavena. Enhanced recruitment of genetically modified CX3CR1-positive human T cells into fractalkine/CX3CL1 expressing tumors: importance of the chemokine gradient. J Immunother Cancer 2016; 4(1): 21
https://doi.org/10.1186/s40425-016-0125-1 pmid: 27096098
69 MH Kershaw, G Wang, JA Westwood, RK Pachynski, HL Tiffany, FM Marincola, E Wang, HA Young, PM Murphy, P Hwu. Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2. Hum Gene Ther 2002; 13(16): 1971–1980
https://doi.org/10.1089/10430340260355374 pmid: 12427307
70 CY Slaney, MH Kershaw, PK Darcy. Trafficking of T cells into tumors. Cancer Res 2014; 74(24): 7168–7174
https://doi.org/10.1158/0008-5472.CAN-14-2458 pmid: 25477332
71 JA Craddock, A Lu, A Bear, M Pule, MK Brenner, CM Rooney, AE Foster. Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b. J Immunother 2010; 33(8): 780–788
https://doi.org/10.1097/CJI.0b013e3181ee6675 pmid: 20842059
72 EK Moon, C Carpenito, J Sun, LC Wang, V Kapoor, J Predina, DJ Powell Jr, JL Riley, CH June, SM Albelda. Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin-specific chimeric antibody receptor. Clin Cancer Res 2011; 17(14): 4719–4730
https://doi.org/10.1158/1078-0432.CCR-11-0351 pmid: 21610146
73 Y Xu, YM Hyun, K Lim, H Lee, RJ Cummings, SA Gerber, S Bae, TY Cho, EM Lord, M Kim. Optogenetic control of chemokine receptor signal and T-cell migration. Proc Natl Acad Sci USA 2014; 111(17): 6371–6376
https://doi.org/10.1073/pnas.1319296111 pmid: 24733886
74 W Peng, Y Ye, BA Rabinovich, C Liu, Y Lou, M Zhang, M Whittington, Y Yang, WW Overwijk, G Lizée, P Hwu. Transduction of tumor-specific T cells with CXCR2 chemokine receptor improves migration to tumor and antitumor immune responses. Clin Cancer Res 2010; 16(22): 5458–5468
https://doi.org/10.1158/1078-0432.CCR-10-0712 pmid: 20889916
75 HD Hickman, GV Reynoso, BF Ngudiankama, SS Cush, J Gibbs, JR Bennink, JW Yewdell. CXCR3 chemokine receptor enables local CD8+ T cell migration for the destruction of virus-infected cells. Immunity 2015; 42(3): 524–537
https://doi.org/10.1016/j.immuni.2015.02.009 pmid: 25769612
76 H Asai, H Fujiwara, J An, T Ochi, Y Miyazaki, K Nagai, S Okamoto, J Mineno, K Kuzushima, H Shiku, H Inoue, M Yasukawa. Co-introduced functional CCR2 potentiates in vivo anti-lung cancer functionality mediated by T cells double gene-modified to express WT1-specific T-cell receptor. PLoS One 2013; 8(2): e56820
https://doi.org/10.1371/journal.pone.0056820 pmid: 23441216
77 N Müller, S Michen, S Tietze, K Töpfer, A Schulte, K Lamszus, M Schmitz, G Schackert, I Pastan, A Temme. Engineering NK cells modified with an EGFRvIII-specific chimeric antigen receptor to overexpress CXCR4 improves immunotherapy of CXCL12/SDF-1a-secreting glioblastoma. J Immunother 2015; 38(5): 197–210
https://doi.org/10.1097/CJI.0000000000000082 pmid: 25962108
78 A Di Stasi, B De Angelis, CM Rooney, L Zhang, A Mahendravada, AE Foster, HE Heslop, MK Brenner, G Dotti, B Savoldo. T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood 2009; 113(25): 6392–6402
https://doi.org/10.1182/blood-2009-03-209650 pmid: 19377047
79 LM Whilding, L Halim, B Draper, AC Parente-Pereira, T Zabinski, DM Davies, J Maher. CAR T-cells targeting the integrin avb6 and co-expressing the chemokine receptor CXCR2 demonstrate enhanced homing and efficacy against several solid malignancies. Cancers (Basel) 2019; 11(5): E674
https://doi.org/10.3390/cancers11050674 pmid: 31091832
80 CP Duong, CS Yong, MH Kershaw, CY Slaney, PK Darcy. Cancer immunotherapy utilizing gene-modified T cells: from the bench to the clinic. Mol Immunol 2015; 67(2 Pt A): 46–57
https://doi.org/10.1016/j.molimm.2014.12.009 pmid: 25595028
81 A Kunert, T Straetemans, C Govers, C Lamers, R Mathijssen, S Sleijfer, R Debets. TCR-engineered T cells meet new challenges to treat solid tumors: choice of antigen, T cell fitness, and sensitization of tumor milieu. Front Immunol 2013; 4: 363
https://doi.org/10.3389/fimmu.2013.00363 pmid: 24265631
82 I Melero, A Rouzaut, GT Motz, G Coukos. T-cell and NK-cell infiltration into solid tumors: a key limiting factor for efficacious cancer immunotherapy. Cancer Discov 2014; 4(5): 522–526
https://doi.org/10.1158/2159-8290.CD-13-0985 pmid: 24795012
83 ST Kim, H Jeong, OH Woo, JH Seo, A Kim, ES Lee, SW Shin, YH Kim, JS Kim, KH Park. Tumor-infiltrating lymphocytes, tumor characteristics, and recurrence in patients with early breast cancer. Am J Clin Oncol 2013; 36(3): 224–231
https://doi.org/10.1097/COC.0b013e3182467d90 pmid: 22495453
84 J Galon, A Costes, F Sanchez-Cabo, A Kirilovsky, B Mlecnik, C Lagorce-Pagès, M Tosolini, M Camus, A Berger, P Wind, F Zinzindohoué, P Bruneval, PH Cugnenc, Z Trajanoski, WH Fridman, F Pagès. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313(5795): 1960–1964
https://doi.org/10.1126/science.1129139 pmid: 17008531
85 K Adachi, Y Kano, T Nagai, N Okuyama, Y Sakoda, K Tamada. IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nat Biotechnol 2018; 36(4): 346–351
https://doi.org/10.1038/nbt.4086 pmid: 29505028
86 DN Mauri, R Ebner, RI Montgomery, KD Kochel, TC Cheung, GL Yu, S Ruben, M Murphy, RJ Eisenberg, GH Cohen, PG Spear, CF Ware. LIGHT, a new member of the TNF superfamily, and lymphotoxin α are ligands for herpesvirus entry mediator. Immunity 1998; 8(1): 21–30
https://doi.org/10.1016/S1074-7613(00)80455-0 pmid: 9462508
87 K Tamada, K Shimozaki, AI Chapoval, Y Zhai, J Su, SF Chen, SL Hsieh, S Nagata, J Ni, L Chen. LIGHT, a TNF-like molecule, costimulates T cell proliferation and is required for dendritic cell-mediated allogeneic T cell response. J Immunol 2000; 164(8): 4105–4110
https://doi.org/10.4049/jimmunol.164.8.4105 pmid: 10754304
88 Y Morel, JM Schiano de Colella, J Harrop, KC Deen, SD Holmes, TA Wattam, SS Khandekar, A Truneh, RW Sweet, JA Gastaut, D Olive, RT Costello. Reciprocal expression of the TNF family receptor herpes virus entry mediator and its ligand LIGHT on activated T cells: LIGHT down-regulates its own receptor. J Immunol 2000; 165(8): 4397–4404
https://doi.org/10.4049/jimmunol.165.8.4397 pmid: 11035077
89 CF Ware. Network communications: lymphotoxins, LIGHT, and TNF. Annu Rev Immunol 2005; 23(1): 787–819
https://doi.org/10.1146/annurev.immunol.23.021704.115719 pmid: 15771586
90 Y Wang, M Zhu, M Miller, YX Fu. Immunoregulation by tumor necrosis factor superfamily member LIGHT. Immunol Rev 2009; 229(1): 232–243
https://doi.org/10.1111/j.1600-065X.2009.00762.x pmid: 19426225
91 YX Fu, DD Chaplin. Development and maturation of secondary lymphoid tissues. Annu Rev Immunol 1999; 17(1): 399–433
https://doi.org/10.1146/annurev.immunol.17.1.399 pmid: 10358764
92 P Yu, YX Fu. Targeting tumors with LIGHT to generate metastasis-clearing immunity. Cytokine Growth Factor Rev 2008; 19(3-4): 285–294
https://doi.org/10.1016/j.cytogfr.2008.04.004 pmid: 18508404
93 P Yu, Y Lee, W Liu, RK Chin, J Wang, Y Wang, A Schietinger, M Philip, H Schreiber, YX Fu. Priming of naive T cells inside tumors leads to eradication of established tumors. Nat Immunol 2004; 5(2): 141–149
https://doi.org/10.1038/ni1029 pmid: 14704792
94 P Yu, Y Lee, Y Wang, X Liu, S Auh, TF Gajewski, H Schreiber, Z You, C Kaynor, X Wang, YX Fu. Targeting the primary tumor to generate CTL for the effective eradication of spontaneous metastases. J Immunol 2007; 179(3): 1960–1968
https://doi.org/10.4049/jimmunol.179.3.1960 pmid: 17641063
95 H Tang, Y Wang, LK Chlewicki, Y Zhang, J Guo, W Liang, J Wang, X Wang, YX Fu. Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade. Cancer Cell 2016; 30(3): 500
https://doi.org/10.1016/j.ccell.2016.08.011 pmid: 27622338
96 RJ Armitage, WC Fanslow, L Strockbine, TA Sato, KN Clifford, BM Macduff, DM Anderson, SD Gimpel, T Davis-Smith, CR Maliszewski, EA Clark, CA Smith, KH Grabstein, D Cosman, MK Spriggs. Molecular and biological characterization of a murine ligand for CD40. Nature 1992; 357(6373): 80–82
https://doi.org/10.1038/357080a0 pmid: 1374165
97 M Armant, R Armitage, N Boiani, G Delespesse, M Sarfati. Functional CD40 ligand expression on T lymphocytes in the absence of T cell receptor engagement: involvement in interleukin-2-induced interleukin-12 and interferon-gamma production. Eur J Immunol 1996; 26(7): 1430–1434
https://doi.org/10.1002/eji.1830260705 pmid: 8766543
98 R Bhadra, JP Gigley, IA Khan. Cutting edge: CD40-CD40 ligand pathway plays a critical CD8-intrinsic and-extrinsic role during rescue of exhausted CD8 T cells. J Immunol 2011; 187(9): 4421–4425
https://doi.org/10.4049/jimmunol.1102319 pmid: 21949017
99 C Bourgeois, B Rocha, C Tanchot. A role for CD40 expression on CD8+ T cells in the generation of CD8+ T cell memory. Science 2002; 297(5589): 2060–2063
https://doi.org/10.1126/science.1072615 pmid: 12242444
100 M Frentsch, R Stark, N Matzmohr, S Meier, S Durlanik, AR Schulz, U Stervbo, K Jürchott, F Gebhardt, G Heine, MA Reuter, MR Betts, D Busch, A Thiel. CD40L expression permits CD8+ T cells to execute immunologic helper functions. Blood 2013; 122(3): 405–412
https://doi.org/10.1182/blood-2013-02-483586 pmid: 23719298
101 Y Liu, M Qureshi, J Xiang. Antitumor immune responses derived from transgenic expression of CD40 ligand in myeloma cells. Cancer Biother Radiopharm 2002; 17(1): 11–18
https://doi.org/10.1089/10849780252824028 pmid: 11915168
102 Y Liu, D Xia, F Li, C Zheng, J Xiang. Intratumoral administration of immature dendritic cells following the adenovirus vector encoding CD40 ligand elicits significant regression of established myeloma. Cancer Gene Ther 2005; 12(2): 122–132
https://doi.org/10.1038/sj.cgt.7700757 pmid: 15565183
103 U Schönbeck, P Libby. The CD40/CD154 receptor/ligand dyad. Cell Mol Life Sci 2001; 58(1): 4–43
https://doi.org/10.1007/PL00000776 pmid: 11229815
104 T Elmetwali, LS Young, DH Palmer. CD40 ligand-induced carcinoma cell death: a balance between activation of TNFR-associated factor (TRAF) 3-dependent death signals and suppression of TRAF6-dependent survival signals. J Immunol 2010; 184(2): 1111–1120
https://doi.org/10.4049/jimmunol.0900528 pmid: 20008286
105 A Angelou, E Antoniou, N Garmpis, C Damaskos, S Theocharis, GA Margonis. The role of soluble CD40L ligand in human carcinogenesis. Anticancer Res 2018; 38(5): 3199–3201
pmid: 29715163
106 K Kato, MJ Cantwell, S Sharma, TJ Kipps. Gene transfer of CD40-ligand induces autologous immune recognition of chronic lymphocytic leukemia B cells. J Clin Invest 1998; 101(5): 1133–1141
https://doi.org/10.1172/JCI1472 pmid: 9486984
107 RH Vonderheide, MJ Glennie. Agonistic CD40 antibodies and cancer therapy. Clin Cancer Res 2013; 19(5): 1035–1043
https://doi.org/10.1158/1078-0432.CCR-12-2064 pmid: 23460534
108 RH Vonderheide, JM Burg, R Mick, JA Trosko, D Li, MN Shaik, AW Tolcher, O Hamid. Phase I study of the CD40 agonist antibody CP-870,893 combined with carboplatin and paclitaxel in patients with advanced solid tumors. OncoImmunology 2013; 2(1): e23033
https://doi.org/10.4161/onci.23033 pmid: 23483678
109 GL Beatty, EG Chiorean, MP Fishman, B Saboury, UR Teitelbaum, W Sun, RD Huhn, W Song, D Li, LL Sharp, DA Torigian, PJ O’Dwyer, RH Vonderheide. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 2011; 331(6024): 1612–1616
https://doi.org/10.1126/science.1198443 pmid: 21436454
110 WG Wierda, MJ Cantwell, SJ Woods, LZ Rassenti, CE Prussak, TJ Kipps. CD40-ligand (CD154) gene therapy for chronic lymphocytic leukemia. Blood 2000; 96(9): 2917–2924
https://doi.org/10.1182/blood.V96.9.2917.h8002917_2917_2924 pmid: 11049967
111 WG Wierda, JE Castro, R Aguillon, D Sampath, A Jalayer, J McMannis, CE Prussak, M Keating, TJ Kipps. A phase I study of immune gene therapy for patients with CLL using a membrane-stable, humanized CD154. Leukemia 2010; 24(11): 1893–1900
https://doi.org/10.1038/leu.2010.191 pmid: 20882050
112 JE Castro, J Melo-Cardenas, M Urquiza, JS Barajas-Gamboa, RS Pakbaz, TJ Kipps. Gene immunotherapy of chronic lymphocytic leukemia: a phase I study of intranodally injected adenovirus expressing a chimeric CD154 molecule. Cancer Res 2012; 72(12): 2937–2948
https://doi.org/10.1158/0008-5472.CAN-11-3368 pmid: 22505652
113 KJ Curran, BA Seinstra, Y Nikhamin, R Yeh, Y Usachenko, DG van Leeuwen, T Purdon, HJ Pegram, RJ Brentjens. Enhancing antitumor efficacy of chimeric antigen receptor T cells through constitutive CD40L expression. Mol Ther 2015; 23(4): 769–778
https://doi.org/10.1038/mt.2015.4 pmid: 25582824
114 NF Kuhn, TJ Purdon, DG van Leeuwen, AV Lopez, KJ Curran, AF Daniyan, RJ Brentjens. CD40 ligand-modified chimeric antigen receptor T cells enhance antitumor function by eliciting an endogenous antitumor response. Cancer Cell 2019; 35(3): 473–488.e6
https://doi.org/10.1016/j.ccell.2019.02.006
115 B Heyman, Y Yang. Chimeric antigen receptor T cell therapy for solid tumors: current status, obstacles and future strategies. Cancers (Basel) 2019; 11(2): E191
https://doi.org/10.3390/cancers11020191 pmid: 30736355
116 DH Yoon, MJ Osborn, J Tolar, CJ Kim. Incorporation of immune checkpoint blockade into chimeric antigen receptor T clls (CAR-Ts): combination or built-in CAR-T. Int J Mol Sci 2018; 19(2): E340
https://doi.org/10.3390/ijms19020340 pmid: 29364163
117 J Brahmer, KL Reckamp, P Baas, L Crinò, WE Eberhardt, E Poddubskaya, S Antonia, A Pluzanski, EE Vokes, E Holgado, D Waterhouse, N Ready, J Gainor, O Arén Frontera, L Havel, M Steins, MC Garassino, JG Aerts, M Domine, L Paz-Ares, M Reck, C Baudelet, CT Harbison, B Lestini, DR Spigel. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015; 373(2): 123–135
https://doi.org/10.1056/NEJMoa1504627 pmid: 26028407
118 J Larkin, V Chiarion-Sileni, R Gonzalez, JJ Grob, CL Cowey, CD Lao, D Schadendorf, R Dummer, M Smylie, P Rutkowski, PF Ferrucci, A Hill, J Wagstaff, MS Carlino, JB Haanen, M Maio, I Marquez-Rodas, GA McArthur, PA Ascierto, GV Long, MK Callahan, MA Postow, K Grossmann, M Sznol, B Dreno, L Bastholt, A Yang, LM Rollin, C Horak, FS Hodi, JD Wolchok. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015; 373(1): 23–34
https://doi.org/10.1056/NEJMoa1504030 pmid: 26027431
119 RJ Motzer, B Escudier, DF McDermott, S George, HJ Hammers, S Srinivas, SS Tykodi, JA Sosman, G Procopio, ER Plimack, D Castellano, TK Choueiri, H Gurney, F Donskov, P Bono, J Wagstaff, TC Gauler, T Ueda, Y Tomita, FA Schutz, C Kollmannsberger, J Larkin, A Ravaud, JS Simon, LA Xu, IM Waxman, P Sharma; CheckMate 025 Investigators. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 2015; 373(19): 1803–1813
https://doi.org/10.1056/NEJMoa1510665 pmid: 26406148
120 JN Kochenderfer, ME Dudley, SH Kassim, RP Somerville, RO Carpenter, M Stetler-Stevenson, JC Yang, GQ Phan, MS Hughes, RM Sherry, M Raffeld, S Feldman, L Lu, YF Li, LT Ngo, A Goy, T Feldman, DE Spaner, ML Wang, CC Chen, SM Kranick, A Nath, DA Nathan, KE Morton, MA Toomey, SA Rosenberg. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol 2015; 33(6): 540–549
https://doi.org/10.1200/JCO.2014.56.2025 pmid: 25154820
121 JN Brudno, RP Somerville, V Shi, JJ Rose, DC Halverson, DH Fowler, JC Gea-Banacloche, SZ Pavletic, DD Hickstein, TL Lu, SA Feldman, AT Iwamoto, R Kurlander, I Maric, A Goy, BG Hansen, JS Wilder, B Blacklock-Schuver, FT Hakim, SA Rosenberg, RE Gress, JN Kochenderfer. Allogeneic T cells that express an anti-CD19 chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease. J Clin Oncol 2016; 34(10): 1112–1121
https://doi.org/10.1200/JCO.2015.64.5929 pmid: 26811520
122 J Eyquem, J Mansilla-Soto, T Giavridis, SJ van der Stegen, M Hamieh, KM Cunanan, A Odak, M Gönen, M Sadelain. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature 2017; 543(7643): 113–117
https://doi.org/10.1038/nature21405 pmid: 28225754
123 ME Keir, MJ Butte, GJ Freeman, AH Sharpe. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008; 26(1): 677–704
https://doi.org/10.1146/annurev.immunol.26.021607.090331 pmid: 18173375
124 S Li, N Siriwon, X Zhang, S Yang, T Jin, F He, YJ Kim, J Mac, Z Lu, S Wang, X Han, P Wang. Enhanced cancer immunotherapy by chimeric antigen receptor-modified T cells engineered to secrete checkpoint inhibitors. Clin Cancer Res 2017; 23(22): 6982–6992
https://doi.org/10.1158/1078-0432.CCR-17-0867 pmid: 28912137
125 L Kuryk, AW Møller, M Jaderberg. Combination of immunogenic oncolytic adenovirus ONCOS-102 with anti-PD-1 pembrolizumab exhibits synergistic antitumor effect in humanized A2058 melanoma huNOG mouse model. OncoImmunology 2019; 8(2): e1532763
https://doi.org/10.1080/2162402X.2018.1532763 pmid: 30713786
126 H Wang, G Kaur, AI Sankin, F Chen, F Guan, X Zang. Immune checkpoint blockade and CAR-T cell therapy in hematologic malignancies. J Hematol Oncol 2019; 12(1): 59
https://doi.org/10.1186/s13045-019-0746-1 pmid: 31186046
127 AM Li, GE Hucks, AM Dinofia, AE Seif, DT Teachey, D Baniewicz, C Callahan, C Fasano, B McBride, V Gonzalez, F Nazimuddin, DL Porter, SF Lacey, CH June, SA Grupp, SL Maude. Checkpoint inhibitors augment CD19-directed chimeric antigen receptor (CAR) T cell therapy in relapsed B-cell acute lymphoblastic leukemia. American Society of Hematology Annual Meeting. 2018. San Diego, California. Blood 2018; 132 (Supplement 1): 556
https://doi.org/10.1182/blood-2018-99-112572
128 LB John, C Devaud, CP Duong, CS Yong, PA Beavis, NM Haynes, MT Chow, MJ Smyth, MH Kershaw, PK Darcy. Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Cancer Res 2013; 19(20): 5636–5646
https://doi.org/10.1158/1078-0432.CCR-13-0458 pmid: 23873688
129 A Heczey, CU Louis, B Savoldo, O Dakhova, A Durett, B Grilley, H Liu, MF Wu, Z Mei, A Gee, B Mehta, H Zhang, N Mahmood, H Tashiro, HE Heslop, G Dotti, CM Rooney, MK Brenner. CAR T cells administered in combination with lymphodepletion and PD-1 inhibition to patients with neuroblastoma. Mol Ther 2017; 25(9): 2214–2224
https://doi.org/10.1016/j.ymthe.2017.05.012 pmid: 28602436
130 ER Suarez, K Chang, J Sun, J Sui, GJ Freeman, S Signoretti, Q Zhu, WA Marasco. Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model. Oncotarget 2016; 7(23): 34341–34355
https://doi.org/10.18632/oncotarget.9114 pmid: 27145284
131 ME Prosser, CE Brown, AF Shami, SJ Forman, MC Jensen. Tumor PD-L1 co-stimulates primary human CD8+ cytotoxic T cells modified to express a PD1:CD28 chimeric receptor. Mol Immunol 2012; 51(3-4): 263–272
https://doi.org/10.1016/j.molimm.2012.03.023 pmid: 22503210
132 J Ren, X Liu, C Fang, S Jiang, CH June, Y Zhao. Multiplex genome editing to generate universal CAR T Cells resistant to PD1 inhibition. Clin Cancer Res 2017; 23(9): 2255–2266
https://doi.org/10.1158/1078-0432.CCR-16-1300 pmid: 27815355
133 LJ Rupp, K Schumann, KT Roybal, RE Gate, CJ Ye, WA Lim, A Marson. CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells. Sci Rep 2017; 7(1): 737
https://doi.org/10.1038/s41598-017-00462-8 pmid: 28389661
134 W Hu, Z Zi, Y Jin, G Li, K Shao, Q Cai, X Ma, F Wei. CRISPR/Cas9-mediated PD-1 disruption enhances human mesothelin-targeted CAR T cell effector functions. Cancer Immunol Immunother 2019; 68(3): 365–377
https://doi.org/10.1007/s00262-018-2281-2 pmid: 30523370
135 D Vicente, AJ Lee, CS Hall, A Lucci, JE Lee, MP Kim, MHG Katz, MW Hurd, A Maitra, AD Rhim Md, CD Tzeng. Circulating tumor cells and transforming growth factor β in resected pancreatic adenocarcinoma. J Surg Res 2019; 243: 90–99
https://doi.org/10.1016/j.jss.2019.04.090 pmid: 31170555
136 H Roca, MJ Craig, C Ying, ZS Varsos, P Czarnieski, AS Alva, J Hernandez, D Fuller, S Daignault, PN Healy, KJ Pienta. IL-4 induces proliferation in prostate cancer PC3 cells under nutrient-depletion stress through the activation of the JNK-pathway and survivin up-regulation. J Cell Biochem 2012; 113(5): 1569–1580
pmid: 22174091
137 D Achkova, J Maher. Role of the colony-stimulating factor (CSF)/CSF-1 receptor axis in cancer. Biochem Soc Trans 2016; 44(2): 333–341
https://doi.org/10.1042/BST20150245 pmid: 27068937
138 PM Siegel, J Massagué. Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer. Nat Rev Cancer 2003; 3(11): 807–821
https://doi.org/10.1038/nrc1208 pmid: 14557817
139 D Hanahan, RA Weinberg. Hallmarks of cancer: the next generation. Cell 2011; 144(5): 646–674
https://doi.org/10.1016/j.cell.2011.02.013 pmid: 21376230
140 MA Travis, D Sheppard. TGF-b activation and function in immunity. Annu Rev Immunol 2014; 32(1): 51–82
https://doi.org/10.1146/annurev-immunol-032713-120257 pmid: 24313777
141 A Gupta, S Budhu, T Merghoub. One checkpoint may hide another: inhibiting the TGFb signaling pathway enhances immune checkpoint blockade. Hepatobiliary Surg Nutr 2019; 8(3): 289–294
https://doi.org/10.21037/hbsn.2019.01.10 pmid: 31245417
142 A Dahmani, JS Delisle. TGF-b in T cell biology: implications for cancer immunotherapy. Cancers (Basel) 2018; 10(6): E194
https://doi.org/10.3390/cancers10060194 pmid: 29891791
143 SH Wrzesinski, YY Wan, RA Flavell. Transforming growth factor-β and the immune response: implications for anticancer therapy. Clin Cancer Res 2007; 13(18 Pt 1): 5262–5270
https://doi.org/10.1158/1078-0432.CCR-07-1157 pmid: 17875754
144 L Zhang, Z Yu, P Muranski, DC Palmer, NP Restifo, SA Rosenberg, RA Morgan. Inhibition of TGF-b signaling in genetically engineered tumor antigen-reactive T cells significantly enhances tumor treatment efficacy. Gene Ther 2013; 20(5): 575–580
https://doi.org/10.1038/gt.2012.75 pmid: 22972494
145 M Ostroukhova, C Seguin-Devaux, TB Oriss, B Dixon-McCarthy, L Yang, BT Ameredes, TE Corcoran, A Ray. Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF-β and FOXP3. J Clin Invest 2004; 114(1): 28–38
https://doi.org/10.1172/JCI200420509 pmid: 15232609
146 CC Kloss, J Lee, A Zhang, F Chen, JJ Melenhorst, SF Lacey, MV Maus, JA Fraietta, Y Zhao, CH June. Dominant-negative TGF-b receptor enhances PSMA-targeted human CAR T cell proliferation and augments prostate cancer eradication. Mol Ther 2018; 26(7): 1855–1866
https://doi.org/10.1016/j.ymthe.2018.05.003 pmid: 29807781
147 ZL Chang, MH Lorenzini, X Chen, U Tran, NJ Bangayan, YY Chen. Rewiring T-cell responses to soluble factors with chimeric antigen receptors. Nat Chem Biol 2018; 14(3): 317–324
https://doi.org/10.1038/nchembio.2565 pmid: 29377003
148 S Sukumaran, N Watanabe, P Bajgain, K Raja, S Mohammed, WE Fisher, MK Brenner, AM Leen, JF Vera. Enhancing the potency and specificity of engineered T cells for cancer treatment. Cancer Discov 2018; 8(8): 972–987
https://doi.org/10.1158/2159-8290.CD-17-1298 pmid: 29880586
149 C Pangault, P Amé-Thomas, P Ruminy, D Rossille, G Caron, M Baia, J De Vos, M Roussel, C Monvoisin, T Lamy, H Tilly, P Gaulard, K Tarte, T Fest. Follicular lymphoma cell niche: identification of a preeminent IL-4-dependent T(FH)-B cell axis. Leukemia 2010; 24(12): 2080–2089
https://doi.org/10.1038/leu.2010.223 pmid: 20944673
150 M Todaro, Y Lombardo, MG Francipane, MP Alea, P Cammareri, F Iovino, AB Di Stefano, C Di Bernardo, A Agrusa, G Condorelli, H Walczak, G Stassi. Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4. Cell Death Differ 2008; 15(4): 762–772
https://doi.org/10.1038/sj.cdd.4402305 pmid: 18202702
151 P Parronchi, M De Carli, R Manetti, C Simonelli, S Sampognaro, MP Piccinni, D Macchia, E Maggi, G Del Prete, S Romagnani. IL-4 and IFN (α and γ) exert opposite regulatory effects on the development of cytolytic potential by Th1 or Th2 human T cell clones. J Immunol 1992; 149(9): 2977–2983
pmid: 1401925
152 JR Schoenborn, CB Wilson. Regulation of interferon-γ during innate and adaptive immune responses. Adv Immunol 2007; 96: 41–101
https://doi.org/10.1016/S0065-2776(07)96002-2 pmid: 17981204
153 RJ Jackson, AJ Ramsay, CD Christensen, S Beaton, DF Hall, IA Ramshaw. Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox. J Virol 2001; 75(3): 1205–1210
https://doi.org/10.1128/JVI.75.3.1205-1210.2001 pmid: 11152493
154 J Brady, S Carotta, RP Thong, CJ Chan, Y Hayakawa, MJ Smyth, SL Nutt. The interactions of multiple cytokines control NK cell maturation. J Immunol 2010; 185(11): 6679–6688
https://doi.org/10.4049/jimmunol.0903354 pmid: 20974986
155 S Wilkie, SE Burbridge, L Chiapero-Stanke, AC Pereira, S Cleary, SJ van der Stegen, JF Spicer, DM Davies, J Maher. Selective expansion of chimeric antigen receptor-targeted T-cells with potent effector function using interleukin-4. J Biol Chem 2010; 285(33): 25538–25544
https://doi.org/10.1074/jbc.M110.127951 pmid: 20562098
156 S Mohammed, S Sukumaran, P Bajgain, N Watanabe, HE Heslop, CM Rooney, MK Brenner, WE Fisher, AM Leen, JF Vera. Improving chimeric antigen receptor-modified T cell function by reversing the immunosuppressive tumor microenvironment of pancreatic cancer. Mol Ther 2017; 25(1): 249–258
https://doi.org/10.1016/j.ymthe.2016.10.016 pmid: 28129119
157 D Abate-Daga, KH Lagisetty, E Tran, Z Zheng, L Gattinoni, Z Yu, WR Burns, AM Miermont, Y Teper, U Rudloff, NP Restifo, SA Feldman, SA Rosenberg, RA Morgan. A novel chimeric antigen receptor against prostate stem cell antigen mediates tumor destruction in a humanized mouse model of pancreatic cancer. Hum Gene Ther 2014; 25(12): 1003–1012
https://doi.org/10.1089/hum.2013.209 pmid: 24694017
158 BM Wolpin, EM O’Reilly, YJ Ko, LS Blaszkowsky, M Rarick, CM Rocha-Lima, P Ritch, E Chan, J Spratlin, T Macarulla, E McWhirter, D Pezet, M Lichinitser, L Roman, A Hartford, K Morrison, L Jackson, M Vincent, L Reyno, M Hidalgo. Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer. Ann Oncol 2013; 24(7): 1792–1801
https://doi.org/10.1093/annonc/mdt066 pmid: 23448807
159 BM Kacinski. CSF-1 and its receptor in ovarian, endometrial and breast cancer. Ann Med 1995; 27(1): 79–85
https://doi.org/10.3109/07853899509031941 pmid: 7742005
160 HO Smith, PS Anderson, DY Kuo, GL Goldberg, CL DeVictoria, CA Boocock, JG Jones, CD Runowicz, ER Stanley, JW Pollard. The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma. Clin Cancer Res 1995; 1(3): 313–325
pmid: 9815987
161 ER Stanley, KL Berg, DB Einstein, PS Lee, FJ Pixley, Y Wang, YG Yeung. Biology and action of colony-stimulating factor-1. Mol Reprod Dev 1997; 46(1): 4–10
https://doi.org/10.1002/(SICI)1098-2795(199701)46:1<4::AID-MRD2>3.0.CO;2-V pmid: 8981357
162 AS Lo, JR Taylor, F Farzaneh, DM Kemeny, NJ Dibb, J Maher. Harnessing the tumour-derived cytokine, CSF-1, to co-stimulate T-cell growth and activation. Mol Immunol 2008; 45(5): 1276–1287
https://doi.org/10.1016/j.molimm.2007.09.010 pmid: 17950877
163 SJ Russell, GN Barber. Oncolytic viruses as antigen-agnostic cancer vaccines. Cancer Cell 2018; 33(4): 599–605
https://doi.org/10.1016/j.ccell.2018.03.011 pmid: 29634947
164 SJ Russell, KW Peng, JC Bell. Oncolytic virotherapy. Nat Biotechnol 2012; 30(7): 658–670
https://doi.org/10.1038/nbt.2287 pmid: 22781695
165 BA Keller, JC Bell. Oncolytic viruses-immunotherapeutics on the rise. J Mol Med (Berl) 2016; 94(9): 979–991
https://doi.org/10.1007/s00109-016-1453-9 pmid: 27492706
166 L Russell, KW Peng. The emerging role of oncolytic virus therapy against cancer. Chin Clin Oncol 2018; 7(2): 16
https://doi.org/10.21037/cco.2018.04.04 pmid: 29764161
167 M Bauzon, T Hermiston. Armed therapeutic viruses — a disruptive therapy on the horizon of cancer immunotherapy. Front Immunol 2014; 5: 74
https://doi.org/10.3389/fimmu.2014.00074 pmid: 24605114
168 S Guedan, JJ Rojas, A Gros, E Mercade, M Cascallo, R Alemany. Hyaluronidase expression by an oncolytic adenovirus enhances its intratumoral spread and suppresses tumor growth. Mol Ther 2010; 18(7): 1275–1283
https://doi.org/10.1038/mt.2010.79 pmid: 20442708
169 S Guedan, D Grases, JJ Rojas, A Gros, F Vilardell, R Vile, E Mercade, M Cascallo, R Alemany. GALV expression enhances the therapeutic efficacy of an oncolytic adenovirus by inducing cell fusion and enhancing virus distribution. Gene Ther 2012; 19(11): 1048–1057
https://doi.org/10.1038/gt.2011.184 pmid: 22113313
170 CA Fajardo, S Guedan, LA Rojas, R Moreno, M Arias-Badia, J de Sostoa, CH June, R Alemany. Oncolytic adenoviral delivery of an EGFR-targeting T-cell engager improves antitumor efficacy. Cancer Res 2017; 77(8): 2052–2063
https://doi.org/10.1158/0008-5472.CAN-16-1708 pmid: 28143835
171 JJ Cody, JT Douglas. Armed replicating adenoviruses for cancer virotherapy. Cancer Gene Ther 2009; 16(6): 473–488
https://doi.org/10.1038/cgt.2009.3 pmid: 19197323
172 PK Bommareddy, M Shettigar, HL Kaufman. Integrating oncolytic viruses in combination cancer immunotherapy. Nat Rev Immunol 2018; 18(8): 498–513
https://doi.org/10.1038/s41577-018-0014-6 pmid: 29743717
173 K Twumasi-Boateng, JL Pettigrew, YYE Kwok, JC Bell, BH Nelson. Oncolytic viruses as engineering platforms for combination immunotherapy. Nat Rev Cancer 2018; 18(7): 419–432
https://doi.org/10.1038/s41568-018-0009-4 pmid: 29695749
174 A Ribas, R Dummer, I Puzanov, A VanderWalde, RHI Andtbacka, O Michielin, AJ Olszanski, J Malvehy, J Cebon, E Fernandez, JM Kirkwood, TF Gajewski, L Chen, KS Gorski, AA Anderson, SJ Diede, ME Lassman, J Gansert, FS Hodi, GV Long. Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy. Cell 2017; 170(6): 1109–1119.e10
https://doi.org/10.1016/j.cell.2017.08.027
175 J Chesney, I Puzanov, F Collichio, P Singh, MM Milhem, J Glaspy, O Hamid, M Ross, P Friedlander, C Garbe, TF Logan, A Hauschild, C Lebbé, L Chen, JJ Kim, J Gansert, RHI Andtbacka, HL Kaufman. Randomized, open-label phase II study evaluating the efficacy and safety of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone in patients with advanced, unresectable melanoma. J Clin Oncol 2018; 36(17): 1658–1667
https://doi.org/10.1200/JCO.2017.73.7379 pmid: 28981385
176 JF Carew, DA Kooby, MW Halterman, SH Kim, HJ Federoff, Y Fong. A novel approach to cancer therapy using an oncolytic herpes virus to package amplicons containing cytokine genes. Mol Ther 2001; 4(3): 250–256
https://doi.org/10.1006/mthe.2001.0448 pmid: 11545616
177 KB Stephenson, NG Barra, E Davies, AA Ashkar, BD Lichty. Expressing human interleukin-15 from oncolytic vesicular stomatitis virus improves survival in a murine metastatic colon adenocarcinoma model through the enhancement of anti-tumor immunity. Cancer Gene Ther 2012; 19(4): 238–246
https://doi.org/10.1038/cgt.2011.81 pmid: 22158521
178 J Li, M O’Malley, J Urban, P Sampath, ZS Guo, P Kalinski, SH Thorne, DL Bartlett. Chemokine expression from oncolytic vaccinia virus enhances vaccine therapies of cancer. Mol Ther 2011; 19(4): 650–657
https://doi.org/10.1038/mt.2010.312 pmid: 21266959
179 JD Dias, O Hemminki, I Diaconu, M Hirvinen, A Bonetti, K Guse, S Escutenaire, A Kanerva, S Pesonen, A Löskog, V Cerullo, A Hemminki. Targeted cancer immunotherapy with oncolytic adenovirus coding for a fully human monoclonal antibody specific for CTLA-4. Gene Ther 2012; 19(10): 988–998
https://doi.org/10.1038/gt.2011.176 pmid: 22071969
180 CE Engeland, C Grossardt, R Veinalde, S Bossow, D Lutz, JK Kaufmann, I Shevchenko, V Umansky, DM Nettelbeck, W Weichert, D Jäger, C von Kalle, G Ungerechts. CTLA-4 and PD-L1 checkpoint blockade enhances oncolytic measles virus therapy. Mol Ther 2014; 22(11): 1949–1959
https://doi.org/10.1038/mt.2014.160 pmid: 25156126
181 P Kleinpeter, L Fend, C Thioudellet, M Geist, N Sfrontato, V Koerper, C Fahrner, D Schmitt, M Gantzer, C Remy-Ziller, R Brandely, D Villeval, K Rittner, N Silvestre, P Erbs, L Zitvogel, E Quéméneur, X Préville, JB Marchand. Vectorization in an oncolytic vaccinia virus of an antibody, a Fab and a scFv against programmed cell death-1 (PD-1) allows their intratumoral delivery and an improved tumor-growth inhibition. OncoImmunology 2016; 5(10): e1220467
https://doi.org/10.1080/2162402X.2016.1220467 pmid: 27853644
182 K Watanabe, Y Luo, T Da, S Guedan, M Ruella, J Scholler, B Keith, RM Young, B Engels, S Sorsa, M Siurala, R Havunen, S Tähtinen, A Hemminki, CH June. Pancreatic cancer therapy with combined mesothelin-redirected chimeric antigen receptor T cells and cytokine-armed oncolytic adenoviruses. JCI Insight 2018; 3(7): 99573
https://doi.org/10.1172/jci.insight.99573 pmid: 29618658
183 EK Moon, LS Wang, K Bekdache, RC Lynn, A Lo, SH Thorne, SM Albelda. Intra-tumoral delivery of CXCL11 via a vaccinia virus, but not by modified T cells, enhances the efficacy of adoptive T cell therapy and vaccines. OncoImmunology 2018; 7(3): e1395997
https://doi.org/10.1080/2162402X.2017.1395997 pmid: 29399394
184 BD Lichty, CJ Breitbach, DF Stojdl, JC Bell. Going viral with cancer immunotherapy. Nat Rev Cancer 2014; 14(8): 559–567
https://doi.org/10.1038/nrc3770 pmid: 24990523
185 K Tanoue, A Rosewell Shaw, N Watanabe, C Porter, B Rana, S Gottschalk, M Brenner, M Suzuki. Armed oncolytic adenovirus-expressing PD-L1 mini-body enhances antitumor effects of chimeric antigen receptor T cells in solid tumors. Cancer Res 2017; 77(8): 2040–2051
https://doi.org/10.1158/0008-5472.CAN-16-1577 pmid: 28235763
186 A Rosewell Shaw, CE Porter, N Watanabe, K Tanoue, A Sikora, S Gottschalk, MK Brenner, M Suzuki. Adenovirotherapy delivering cytokine and checkpoint inhibitor augments CAR T cells against metastatic head and neck cancer. Mol Ther 2017; 25(11): 2440–2451
https://doi.org/10.1016/j.ymthe.2017.09.010 pmid: 28974431
187 J Qiao, H Wang, T Kottke, RM Diaz, C Willmon, A Hudacek, J Thompson, K Parato, J Bell, J Naik, J Chester, P Selby, K Harrington, A Melcher, RG Vile. Loading of oncolytic vesicular stomatitis virus onto antigen-specific T cells enhances the efficacy of adoptive T-cell therapy of tumors. Gene Ther 2008; 15(8): 604–616
https://doi.org/10.1038/sj.gt.3303098 pmid: 18305577
188 C Cole, J Qiao, T Kottke, RM Diaz, A Ahmed, L Sanchez-Perez, G Brunn, J Thompson, J Chester, RG Vile. Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells. Nat Med 2005; 11(10): 1073–1081
https://doi.org/10.1038/nm1297 pmid: 16170322
189 H VanSeggelen, DG Tantalo, A Afsahi, JA Hammill, JL Bramson. Chimeric antigen receptor-engineered T cells as oncolytic virus carriers. Mol Ther Oncolytics 2015; 2: 15014
https://doi.org/10.1038/mto.2015.14 pmid: 27119109
190 AC Parente-Pereira, LM Whilding, N Brewig, SJ van der Stegen, DM Davies, S Wilkie, MC van Schalkwyk, S Ghaem-Maghami, J Maher. Synergistic chemoimmunotherapy of epithelial ovarian cancer using ErbB-retargeted T cells combined with carboplatin. J Immunol 2013; 191(5): 2437–2445
https://doi.org/10.4049/jimmunol.1301119 pmid: 23898037
191 P Muranski, A Boni, C Wrzesinski, DE Citrin, SA Rosenberg, R Childs, NP Restifo. Increased intensity lymphodepletion and adoptive immunotherapy — how far can we go? Nat Clin Pract Oncol 2006; 3(12): 668–681
https://doi.org/10.1038/ncponc0666 pmid: 17139318
192 KJ Curran, S Margossian, NA Kernan, LB Silverman, DA Williams, NN Shukla, R Kobos, C Forlenza, P Steinherz, S Prockop, F Boulad, B Spitzer, MI Cancio, JJ Boelens, AL Kung, VZ Szenes, J Park, CS Sauter, G Heller, X Wang, B Senechal, RJ O’Reilly, I Riviere, M Sadelain, RJ Brentjens. Toxicity and response following CD19-specific CAR T cells in pediatric/young adult relapsed/refractory B-ALL. Blood 2019; 134(26): 2361–2368
https://doi.org/10.1182/blood.2019001641
193 AV Hirayama, J Gauthier, KA Hay, JM Voutsinas, Q Wu, BS Pender, RM Hawkins, A Vakil, RN Steinmetz, SR Riddell, DG Maloney, CJ Turtle. High rate of durable complete remission in follicular lymphoma after CD19 CAR-T cell immunotherapy. Blood 2019; 134(7): 636–640
https://doi.org/10.1182/blood.2019000905 pmid: 31648294
194 AR Haas, JL Tanyi, MH O’Hara, WL Gladney, SF Lacey, DA Torigian, MC Soulen, L Tian, M McGarvey, AM Nelson, CS Farabaugh, E Moon, BL Levine, JJ Melenhorst, G Plesa, CH June, SM Albelda, GL Beatty. Phase I study of lentiviral-transduced chimeric antigen receptor-modified T cells recognizing mesothelin in advanced solid cancers. Mol Ther 2019; 27(11): 1919–1929
https://doi.org/10.1016/j.ymthe.2019.07.015 pmid: 31420241
195 JN Brudno, I Maric, SD Hartman, JJ Rose, M Wang, N Lam, M Stetler-Stevenson, D Salem, C Yuan, S Pavletic, JA Kanakry, SA Ali, L Mikkilineni, SA Feldman, DF Stroncek, BG Hansen, J Lawrence, R Patel, F Hakim, RE Gress, JN Kochenderfer. T cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J Clin Oncol 2018; 36(22): 2267–2280
https://doi.org/10.1200/JCO.2018.77.8084 pmid: 29812997
196 WY Zhang, Y Liu, Y Wang, J Nie, YL Guo, CM Wang, HR Dai, QM Yang, ZQ Wu, WD Han. Excessive activated T-cell proliferation after anti-CD19 CAR T-cell therapy. Gene Ther 2018; 25(3): 198–204
https://doi.org/10.1038/s41434-017-0001-8 pmid: 29599530
197 K Feng, Y Liu, Y Guo, J Qiu, Z Wu, H Dai, Q Yang, Y Wang, W Han. Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers. Protein Cell 2018; 9(10): 838–847
https://doi.org/10.1007/s13238-017-0440-4 pmid: 28710747
198 RJ Brentjens, I Rivière, JH Park, ML Davila, X Wang, J Stefanski, C Taylor, R Yeh, S Bartido, O Borquez-Ojeda, M Olszewska, Y Bernal, H Pegram, M Przybylowski, D Hollyman, Y Usachenko, D Pirraglia, J Hosey, E Santos, E Halton, P Maslak, D Scheinberg, J Jurcic, M Heaney, G Heller, M Frattini, M Sadelain. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood 2011; 118(18): 4817–4828
https://doi.org/10.1182/blood-2011-04-348540 pmid: 21849486
199 M Shevtsov, H Sato, G Multhoff, A Shibata. Novel approaches to improve the efficacy of immuno-radiotherapy. Front Oncol 2019; 9: 156
https://doi.org/10.3389/fonc.2019.00156 pmid: 30941308
200 I Minn, SP Rowe, MG Pomper. Enhancing CAR T-cell therapy through cellular imaging and radiotherapy. Lancet Oncol 2019; 20(8): e443–e451
https://doi.org/10.1016/S1470-2045(19)30461-9 pmid: 31364596
201 T Weiss, M Weller, M Guckenberger, CL Sentman, P Roth. NKG2D-based CAR T cells and radiotherapy exert synergistic efficacy in glioblastoma. Cancer Res 2018; 78(4): 1031–1043
https://doi.org/10.1158/0008-5472.CAN-17-1788 pmid: 29222400
202 C DeSelm, ML Palomba, J Yahalom, M Hamieh, J Eyquem, VK Rajasekhar, M Sadelain. Low-dose radiation conditioning enables CAR T cells to mitigate antigen escape. Mol Ther 2018; 26(11): 2542–2552
https://doi.org/10.1016/j.ymthe.2018.09.008 pmid: 30415658
203 C Qu, N Ping, Q Wu, L Kang, F Xia, L Yu, D Wu, Z Jin. Radiotherapy priming chimeric antigen receptor T cell therapy is a safe and promising approach in relapsed/refractory diffuse large B cell lymphoma patients with high tumor burden. Blood 2018; 132(Suppl 1): 2961
204 TT Smith, HF Moffett, SB Stephan, CF Opel, AG Dumigan, X Jiang, VG Pillarisetty, SPS Pillai, KD Wittrup, MT Stephan. Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors. J Clin Invest 2017; 127(6): 2176–2191
https://doi.org/10.1172/JCI87624 pmid: 28436934
205 SA Bencherif, R Warren Sands, OA Ali, WA Li, SA Lewin, TM Braschler, TY Shih, CS Verbeke, D Bhatta, G Dranoff, DJ Mooney. Injectable cryogel-based whole-cell cancer vaccines. Nat Commun 2015; 6(1): 7556
https://doi.org/10.1038/ncomms8556 pmid: 26265369
206 J Kim, WA Li, Y Choi, SA Lewin, CS Verbeke, G Dranoff, DJ Mooney. Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy. Nat Biotechnol 2015; 33(1): 64–72
https://doi.org/10.1038/nbt.3071 pmid: 25485616
207 BA Pulaski, S Ostrand-Rosenberg. Mouse 4T1 breast tumor model. Curr Protoc Immunol, 2001. Chapter 20: Unit 20.2
https://doi.org/10.1002/0471142735.im2002s39
208 LC Bailey-Downs, JE Thorpe, BC Disch, A Bastian, PJ Hauser, T Farasyn, WL Berry, RE Hurst, MA Ihnat. Development and characterization of a preclinical model of breast cancer lung micrometastatic to macrometastatic progression. PLoS One 2014; 9(5): e98624
https://doi.org/10.1371/journal.pone.0098624 pmid: 24878664
209 F Zhang, SB Stephan, CI Ene, TT Smith, EC Holland, MT Stephan. Nanoparticles that reshape the tumor milieu create a therapeutic window for effective T-cell therapy in solid malignancies. Cancer Res 2018; 78(13): 3718–3730
https://doi.org/10.1158/0008-5472.CAN-18-0306 pmid: 29760047
210 D Hambardzumyan, NM Amankulor, KY Helmy, OJ Becher, EC Holland. Modeling adult gliomas using RCAS/t-va technology. Transl Oncol 2009; 2(2): 89–95
https://doi.org/10.1593/tlo.09100 pmid: 19412424
211 M Weller, N Butowski, DD Tran, LD Recht, M Lim, H Hirte, L Ashby, L Mechtler, SA Goldlust, F Iwamoto, J Drappatz, DM O’Rourke, M Wong, MG Hamilton, G Finocchiaro, J Perry, W Wick, J Green, Y He, CD Turner, MJ Yellin, T Keler, TA Davis, R Stupp, JH Sampson; ACT IV trial investigators. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol 2017; 18(10): 1373–1385
https://doi.org/10.1016/S1470-2045(17)30517-X pmid: 28844499
212 N Ahmed, V Brawley, M Hegde, K Bielamowicz, M Kalra, D Landi, C Robertson, TL Gray, O Diouf, A Wakefield, A Ghazi, C Gerken, Z Yi, A Ashoori, MF Wu, H Liu, C Rooney, G Dotti, A Gee, J Su, Y Kew, D Baskin, YJ Zhang, P New, B Grilley, M Stojakovic, J Hicks, SZ Powell, MK Brenner, HE Heslop, R Grossman, WS Wels, S Gottschalk. HER2-specific chimeric antigen receptor-modified virus-specific T cells for progressive glioblastoma: a phase 1 dose-escalation trial. JAMA Oncol 2017; 3(8): 1094–1101
https://doi.org/10.1001/jamaoncol.2017.0184 pmid: 28426845
[1] Jianqing Mi, Jie Xu, Jianfeng Zhou, Weili Zhao, Zhu Chen, J. Joseph Melenhorst, Saijuan Chen. CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies[J]. Front. Med., 2021, 15(6): 783-804.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed