Can We Use CAR-T Cells to Overcome Immunosuppression in Solid Tumours?

Area of Science:

• Immunology
• Synthetic Biology
• Oncology

Background:

• Chimeric antigen receptor (CAR)-T-cell therapy has transformed hematological cancer treatment.
• Solid tumor treatment with CAR-T cells is hindered by the immunosuppressive tumor microenvironment (TME), poor antigen specificity, and infiltration barriers.

Purpose of the Study:

• To explore the potential of adapting CAR-T cells to overcome solid tumor immunosuppression.
• To analyze TME-related challenges and evaluate engineering strategies for enhanced CAR-T cell function.

Main Methods:

• Review of immunological, metabolic, and structural TME challenges.
• Evaluation of engineering strategies: metabolic reprogramming, hypoxia-responsive constructs, checkpoint resistance, and novel delivery systems.
• Analysis of synergistic combination therapies (e.g., with immune checkpoint inhibitors, radiotherapy, oncolytic viruses).

Main Results:

• Engineered "armored" CAR-T cells secreting cytokines (e.g., IL-12, IL-18) can reprogram the TME and restore anti-tumor immunity.
• Preclinical and early clinical studies show promise for enhanced CAR-T cell persistence and function.
• Personalized strategies like bispecific targeting and precision delivery demonstrate potential in overcoming resistance.

Conclusions:

• CAR-T cell therapy holds significant potential for treating solid tumors by overcoming TME-induced immunosuppression.
• Advancements in synthetic immunology offer hope for durable remissions and new treatment paradigms.
• This review provides a roadmap for translating CAR-T cell therapy for solid tumors into clinical reality.