NK Cell-Fc Receptors Advance Tumor Immunotherapy

Immunotherapy has revolutionized the treatment of cancer patients. Among immunotherapeutic approaches, antibodies targeting immune checkpoint inhibitors Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are approved for treatment of metastatic melanoma and are in clinical trials for a variety of other cancers. The contribution of Natural Killer (NK) cells to the efficacy of immune checkpoint inhibitors is becoming more evident. Enhancing both T and NK cell function in cancer could result in a robust and durable response. Along with the ability to directly kill tumor cells, NK cells can mediate antibody-dependent cellular cytotoxicity (ADCC) given the expression of Fragment Crystallizable (Fc) receptors. Promising novel antibodies modified with improved Fc-receptor-mediated functions or Fc-engagers to kill target cells have been tested in pre-clinical models with considerable results. Combination therapies with immune-therapeutic antibodies with enhancers of NK-cell Fc-receptor-mediated function can be exploited to increase the efficacy of these antibodies. Herein, I discuss possible strategies to improve the success of immunotherapy by boosting NK cell function.