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A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy

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Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.

Zui Chen^1,2, Xin Zhou^1,2

¹School of Basic Medicine, Capital Medical University, Beijing 100069, China.

Acta Biochimica Et Biophysica Sinica

|October 24, 2025

Summary

Chimeric antigen receptor (CAR)-T cell therapy shows promise for solid tumors by overcoming barriers like poor infiltration and immunosuppression through novel engineering strategies. These advances aim to improve patient outcomes in solid malignancies.

Keywords:

CAR-T TCR immunotherapy solid tumor

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Area of Science:

Immunology
Cancer Biology
Biotechnology

Background:

T cell receptor (TCR) signaling is crucial for T cell activation.
Chimeric antigen receptor (CAR)-T cell therapy has succeeded in hematologic malignancies but faces challenges in solid tumors.

Purpose of the Study:

To summarize CAR signaling dynamics.
To highlight breakthrough strategies for improving CAR-T cell efficacy in solid tumors.

Main Methods:

Review of current understanding of CAR signaling.
Analysis of novel engineering strategies for CAR-T cells.

Main Results:

Solid tumors present barriers including poor infiltration, immunosuppressive tumor microenvironment (TME), metabolic competition, and antigen heterogeneity.
Strategies include engineering CARs for enhanced signaling, cytokine secretion, epigenetic reprogramming, and synthetic biology approaches.

Conclusions:

Recent advances are narrowing the efficacy gap between liquid and solid tumors for CAR-T cell therapy.
These strategies hold promise for improved clinical outcomes and personalized immunotherapy in solid malignancies.