Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.

Advancements in genetic engineering and synthetic biology have markedly accelerated the development and application of chimeric antigen receptor T (CAR-T) cell therapy for cancer treatment. Despite substantial progress, the treatment of solid tumors remains challenging, with suboptimal clinical outcomes and significant unmet needs. To address these ongoing challenges, considerable efforts are being made to enhance the safety, efficacy, and overall applicability of CAR-T cells therapy. This review outlines the key tumor features that impede CAR-T efficacy, focusing on intrinsic tumor factors and the influence of the microenvironment. We then provide a comprehensive overview of the promising next-generation CAR-T designs and discuss the combinatorial approaches aimed at improving antigen recognition, functional adaptability, and antitumor response, thereby expanding the therapeutic impact of CAR-T cells in solid-tumor settings.