A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma

doi:10.1007/s11684-020-0808-3

Front. Med.

2020, Vol. 14

Issue (6) : 711-725 https://doi.org/10.1007/s11684-020-0808-3

REVIEW

A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma

Houli Zhao^1,^2,³, Yiyun Wang^1,^2,³, Elaine Tan Su Yin^1,^2,³, Kui Zhao⁴, Yongxian Hu^1,^2,³(

), He Huang^1,^2,³(

)

¹. Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China
². Zhejiang Province Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou 310000, China
³. Institute of Hematology, Zhejiang University, Hangzhou 310000, China
⁴. PET-CT Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China

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Abstract

The combination of the immunotherapy (i.e., the use of monoclonal antibodies) and the conventional chemotherapy increases the long-term survival of patients with lymphoma. However, for patients with relapsed or treatment-resistant lymphoma, a novel treatment approach is urgently needed. Chimeric antigen receptor T (CAR-T) cells were introduced as a treatment for these patients. Based on recent clinical data, approximately 50% of patients with relapsed or refractory B-cell lymphoma achieved complete remission after receiving the CD19 CAR-T cell therapy. Moreover, clinical data revealed that some patients remained in remission for more than two years after the CAR-T cell therapy. Other than the CD19-targeted CAR-T, the novel target antigens, such as CD20, CD22, CD30, and CD37, which were greatly expressed on lymphoma cells, were studied under preclinical and clinical evaluations for use in the treatment of lymphoma. Nonetheless, the CAR-T therapy was usually associated with potentially lethal adverse effects, such as the cytokine release syndrome and the neurotoxicity. Therefore, optimizing the structure of CAR, creating new drugs, and combining CAR-T cell therapy with stem cell transplantation are potential solutions to increase the effectiveness of treatment and reduce the toxicity in patients with lymphoma after the CAR-T cell therapy.

Keywords chimeric antigen receptor T (CAR-T) cell lymphoma cytokine release syndrome (CRS) immune effector cell-associated neurotoxicity syndrome (ICANS)

Corresponding Author(s): Yongxian Hu,He Huang

Just Accepted Date: 27 October 2020 Online First Date: 26 November 2020 Issue Date: 24 December 2020

Cite this article:

Houli Zhao,Yiyun Wang,Elaine Tan Su Yin, et al. A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma[J]. Front. Med., 2020, 14(6): 711-725.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-020-0808-3
https://academic.hep.com.cn/fmd/EN/Y2020/V14/I6/711

Fig.1 Generation of CAR structures. (A) First-generation CARs contain antigen-recognizing (scFv), transmembrane, and T cell activation (CD3z) domains. (B) Second-generation CARs, to which the costimulatory domains (CD28 or 4-1BB) are added with respect to the first-generation CAR, show high levels of antitumor activity. (C) Third-generation CARs include two costimulatory domains (CD28 and 4-1BB).

Fig.2 Process of CAR-T cell therapy in clinics. Lymphocytes were collected from patients or donors via the leukapheresis. After T cell enrichment and activation, the CAR gene was transduced into T cells. The CAR-T cells were expanded adequately ex vivo for clinical use. Patients normally received the lymphodepleting chemotherapy prior to the CAR-T cell infusion.

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