Advances and Challenges in CAR-NK Cell Therapy for Tumor Immunotherapy

Abstract

The root cause of tumors lies in genetic mutations. NK cells have shown significant potential in tumor immunotherapy. NK cells possess three anti-tumor mechanisms: direct cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and secretion of cytokines. Compared with traditional αβ T cell therapy, NK cell therapy is safer, and KIR mismatch can enhance its anti-tumor response. CAR-NK cell therapy, through genetic engineering, transfers the synthetic receptor protein CAR into NK cells, enabling precise recognition and killing of tumor cells. The mechanisms by which CAR-NK cells kill tumor cells include the release of cytotoxic granules, induction of apoptosis, and secretion of cytokines. This therapy has remarkable efficacy in treating solid tumors, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia, and has advantages such as broad-spectrum anti-tumor activity, wide cell source, relatively simple preparation, and the ability to be used as a "ready-made" product. However, CAR-NK cell therapy also faces challenges such as limitations on NK cell infiltration by the tumor microenvironment, limited cell sources, and deficiencies in immune checkpoint inhibitors. Combining with traditional therapies such as chemotherapy and radiotherapy or using other biological agents in combination is expected to improve its efficacy. In addition, allogeneic NK cell therapy has been applied in hematopoietic stem cell transplantation and adoptive immunotherapy, although it shows significant efficacy in hematological malignancies, it still needs improvement in the treatment of solid tumors. Overall, NK cell therapy has a promising future, but many difficulties need to be overcome to achieve wider clinical application.