Strategies to Overcome Antigen Heterogeneity in CAR-T Cell Therapy

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2025 Mar 12

PMID 40072049

Authors

Bohan Zhang

Jiawen Wu

Hua Jiang

Min Zhou

Affiliations

Soon will be listed here.

Abstract

Chimeric antigen receptor (CAR) gene-modified T-cell therapy has achieved significant success in the treatment of hematological malignancies. However, this therapy has not yet made breakthroughs in the treatment of solid tumors and still faces issues of resistance and relapse in hematological cancers. A major reason for these problems is the antigenic heterogeneity of tumor tissues. This review outlines the antigenic heterogeneity encountered in CAR-T cell therapy and the corresponding strategies to address it. These strategies include using combination therapy to increase the abundance of target antigens, optimizing the structure of CARs to enhance sensitivity to low-density antigens, developing multi-targeted CAR-T cells, and reprogramming the TME to activate endogenous immunity. These approaches offer new directions for overcoming tumor antigenic heterogeneity in CAR-T cell therapy.

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