CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a sweet success?
10.1007/s11684-021-0901-2
- Author:
Pooria SAFARZADEH KOZANI
1
;
Pouya SAFARZADEH KOZANI
2
;
Fatemeh RAHBARIZADEH
3
Author Information
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. Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, P.O. Box 14115/111, Iran. rahbarif@modares.ac.ir.
- Publication Type:Review
- Keywords:
O-glycans;
adoptive cell therapy;
cancer immunotherapy;
chimeric antigen receptor;
glycosylation;
solid tumors;
tumor-associated antigen
- MeSH:
Antigens, Neoplasm/chemistry*;
Biomarkers, Tumor/metabolism*;
Glycosylation;
Hematologic Neoplasms/drug therapy*;
Humans;
Immunotherapy, Adoptive/methods*;
Male;
Neoplasm Recurrence, Local/metabolism*;
Receptors, Chimeric Antigen;
T-Lymphocytes;
United States
- From:
Frontiers of Medicine
2022;16(3):322-338
- CountryChina
- Language:English
-
Abstract:
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.
