1. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, P.O. Box 14115/111, Iran 2. Department of Medical Biotechnology, Faculty of Paramedicine, Guilan University of Medical Sciences, Rasht, P.O. Box 44771/66595, Iran 3. Research and Development Center of Biotechnology, Tarbiat Modares University, Tehran, P.O. Box 14115/111, Iran
Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.
Astrocytic tumors, malignant mesothelioma, and germ cell tumors
[113,114]
LpMab-2
Podoplanin (with aberrant O-glycosylation or sialylation)
[81]
HMFG2
MUC1 (glycosylation dependent)
HNSCC, pancreatic cancer, breast cancer, and various other
[87,92]
SM3
MUC1 (glycosylation dependent)
adenocarcinomas
[115]
pSM3
Sialyl-T of MUC1
[88]
TAB004
The tumor form of MUC1 (tMUC1)
[89,99]
PankoMAb
Tn glycoform of MUC1
[116]
2D9
Tn glycoform of MUC1
[117]
MY.1E12
Sialylated MUC1
[118,119]
VU-2-G7
Tn glycoform of MUC1
[120]
1B9
T glycoform of MUC1
[117]
5E5
Tn glycoform of MUC1
[121]
PMH1
Tn glycoform of MUC2
Mucinous adenocarcinoma
[108]
6E3
Tn glycoform of MUC4
Epithelial carcinomas
[109]
UN1
Tn glycoform of CD43
Breast cancer, colon cancer, and T-cell leukemia
[110,111]
FDC-6
Tn glycoform of fibronectin
Colon and liver cancers
[112]
B72.3
Sialyl-Tn epitope (expressed on glycoproteins and mucins)
Ovarian cancer, lung adenocarcinoma, and colorectal
[44,101]
CC49
Sialyl-Tn epitope (expressed on glycoproteins and mucins)
cancer
[122]
Tab.1
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