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Updated: Feb 15, 2026
Generation of Human Chimeric Antigen Receptor Regulatory T Cells
Published on: January 3, 2025
New Chimeric Antigen Receptor Design for Solid Tumors
Yuedi Wang1,2, Feifei Luo2,3, Jiao Yang1,2
1Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Abstract:
In recent years, chimeric antigen receptor (CAR) T-cell therapy has become popular in immunotherapy, particularly after its tremendous success in the treatment of lineage-restricted hematologic cancers. However, the application of CAR T-cell therapy for solid tumors has not reached its full potential because of the lack of specific tumor antigens and inhibitory factors in suppressive tumor microenvironment (TME) (e.g., programmed death ligand-1, myeloid-derived suppressor cells, and transforming growth factor-β). In this review, we include some limitations in CAR design, such as tumor heterogeneity, indefinite spatial distance between CAR T-cell and its target cell, and suppressive TME. We also summarize some new approaches to overcome these hurdles, including targeting neoantigens and/or multiple antigens at once and depleting some inhibitory factors.
Insights
Chimeric antigen receptor (CAR) T-cell therapy shows promise for solid tumors. New strategies address challenges like tumor heterogeneity and the suppressive tumor microenvironment (TME) to improve efficacy.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Chimeric antigen receptor (CAR) T-cell therapy has achieved success in hematologic cancers.
- Solid tumor treatment with CAR T-cells is limited by antigen scarcity and a suppressive tumor microenvironment (TME).
- Key TME inhibitory factors include programmed death ligand-1, myeloid-derived suppressor cells, and transforming growth factor-β.
Purpose of the Study:
- To review limitations of CAR T-cell therapy in solid tumors.
- To summarize novel strategies for overcoming these challenges.
Main Methods:
- Review of current literature on CAR T-cell therapy for solid tumors.
- Analysis of CAR design limitations.
- Identification of emerging therapeutic approaches.
Main Results:
- CAR T-cell therapy faces hurdles including tumor heterogeneity, target cell proximity, and TME suppression.
- New approaches focus on targeting neoantigens and multiple antigens.
- Strategies also involve depleting inhibitory factors within the TME.
Conclusions:
- Overcoming TME-related challenges is crucial for advancing CAR T-cell therapy in solid tumors.
- Targeting multiple antigens and neoantigens offers potential for improved specificity.
- Depleting immunosuppressive factors can enhance CAR T-cell function against solid tumors.
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