Progress in cell-based immunotherapies for solid tumors.

The advancement of translational oncology has been driven by the integration of diverse cutting-edge technologies, including cell-based therapies, innovative biomaterials, controlled release systems, nanomedicine, and phototherapy. Among these, cell-based immunotherapies—such as Chimeric Antigen Receptor T-cell (CAR-T) therapy, Natural killer (NK) cell-based therapy, and T-cell receptor-engineered T cell (TCR-T) therapy—represent a transformative frontier in cancer treatment, enabling precise and personalized targeting of tumor cells. Although these approaches have achieved remarkable success in hematologic malignancies, their application to solid tumors remains challenging. Major obstacles include antigen heterogeneity, immunosuppressive tumor microenvironments, limited cellular infiltration, off-target toxicity, and complexities in large-scale manufacturing. CAR-T cell therapy has shown outstanding efficacy in blood cancers but faces significant barriers when applied to solid tumors. NK cell-based therapies offer advantages such as a reduced risk of graft-versus-host disease, yet they encounter similar limitations in tumor penetration and persistence. TCR-T therapies expand the therapeutic scope by recognizing intracellular antigens; however, their effectiveness depends on careful antigen selection to minimize off-target effects. Other cell-based strategies, including tumor-infiltrating lymphocytes (TILs) and induced pluripotent stem cell (iPSC)-derived therapies, have also demonstrated therapeutic potential but require further optimization to enhance durability and overcome immune suppression within the tumor microenvironment. Manufacturing complexity, high production costs, and the need to ensure both safety and efficacy continue to pose significant challenges to clinical translation. Future progress in gene editing, multi-antigen targeting, synthetic biology, development of off-the-shelf allogeneic products, and personalized therapeutic design is expected to help address these limitations. Sustained research and technological innovation will be essential to improving the safety, efficacy, and scalability of cell-based immunotherapies, ultimately enhancing their clinical impact and patient outcomes.