Optimizing CAR-T cell therapy in solid tumors through multi-target and vaccine strategies

Chimeric antigen receptor (CAR) T cells can be used to treat B-cell malignancies and represent a novel approach in cancer immune cell therapy. Although the therapy has shown significant clinical success in treating B-cell malignancies, its efficacy in solid tumors is limited by challenges such as tumor antigen heterogeneity, antigen loss, and immunosuppressive tumor microenvironment. This review understands the shortcomings of CAR-T cell therapy and proposes several optimization strategies to face different dilemmas in treating tumors. Targeting fibroblast activation protein (FAP) to suppress the TME; RNA vaccines that can deliver specific antigens to lymph nodes to activate and expand CAR-T cells to enhance their immune response against solid tumors; and multi-targeting design to target multiple antigens at the same time to effectively mitigate tumor escape due to antigen loss. In addition, this review enumerates the strategies of combining therapies with chemotherapy, radiotherapy, immune checkpoint inhibitors, and co-stimulatory molecules to improve the durability and targeting precision of CAR-T cells and reduce side effects. Thus, this review demonstrates a series of optimized uses of CAR-T cell therapies and improves the efficacy of CAR-T cells in solid tumors. This has important clinical implications for advancing cancer immunotherapy and driving the development of immune cancer in the future.