Application of CAR-T therapy in solid tumors: current opportunities and challenges

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized hematologic malignancy treatment.
• Significant challenges limit CAR-T efficacy in solid tumors, including antigen heterogeneity and the immunosuppressive tumor microenvironment (TME).

Purpose of the Study:

• To systematically review advancements in CAR-T therapy for solid tumors.
• To discuss barriers and emerging strategies for improving CAR-T cell therapy in solid tumors.

Main Methods:

• Systematic review of CAR-T cell therapy for solid tumors (lung, pancreatic, neuroblastoma, breast).
• Analysis of CAR-T cell design evolution (1st-5th generation) and functional modules.
• Discussion of challenges and emerging strategies (2023-2025).

Main Results:

• CAR-T therapy faces barriers like antigen heterogeneity, T-cell exhaustion, and immunosuppressive TME.
• Emerging strategies include bispecific CAR-T cells, regional administration, logic-gated constructs, safety switches, and TME modulation.
• Recent developments show progress in overcoming limitations for solid tumor treatment.

Conclusions:

• Despite challenges, integrated cutting-edge technologies are advancing CAR-T therapy for solid tumors.
• New prospects are emerging for patients with refractory solid malignancies.
• Future directions focus on refining CAR-T applications in solid tumors.