Overcoming solid-tumor barriers: armored CAR-T cell therapy

Chimeric antigen receptor (CAR)-T cell therapy has shown significant clinical benefit in hematologic malignancies but remains less effective in solid tumors due to multiple barriers, including limited tumor infiltration, immunosuppressive microenvironments, and heterogeneity or imperfect specificity in tumor-antigen expression. 'Armoring' CAR-T cells to express chemokine receptors, enzymes that degrade extracellular matrix components, proinflammatory cytokines, or factors that modulate immunosuppressive signals could empower CAR-T cells to overcome barriers associated with solid tumors. However, translating promising preclinical results into reliable clinical benefit for patients with solid tumors remains challenging. This review critically examines emerging CAR-T cell armoring approaches and highlights key translational hurdles and the need for innovations in human-relevant disease models, safety designs, and treatment strategies for effective translation.