Delivering CAR-T cells into solid tumors via hydrogels

Chimeric antigen receptor (CAR)-T cell therapy is a promising form of cancer immunotherapy that genetically modifies a patient's own T cells to express CARs for the specific recognition and eradication of cancer cells. Unfortunately, unlike the impressive advancements it achieves in hematologic cancer treatment, CAR-T cell therapy has encountered obstacles in treating solid tumors such as high cost, inadequate tumor infiltration, and immunosuppressive tumor microenvironment. Recently, the regional administration of CAR-T cells via hydrogel platforms has been investigated as a potential method to not only promote tumor infiltration, cell expansion, and anticancer efficacy of the CAR-T cells but also provide a multifunctional platform to introduce additional therapeutic agents for achieving potentiated cancer therapy. In this perspective, different design strategies of CAR-T cell delivery hydrogels are introduced. Besides, various types of therapeutic agents incorporated in the hydrogel platforms and diverse hydrogel formulations have been discussed. The current challenges and future research directions on CAR-T cell delivery hydrogels are also proposed. It is hoped that this perspective can help future researchers develop new CAR-T cell delivery hydrogels that can effectively fight against solid tumors.