Natural Killer Cells: A Promising Kit in the Adoptive Cell Therapy Toolbox

Simple Summary Adoptive cellular immunotherapy is one of the most effective strategies promising to eliminate tumors. Natural killer (NK) cells gain increasing attention for their stable availability and safety properties. To improve the anti-tumor efficacy of NK cells, multiple genetically engineered NK cellular products have been tested in recent years. In this review, we evaluate the latest research progress on adoptive NK cell therapy with a special focus on their alternative sources and genetic modifications. As an important component of the innate immune system, natural killer (NK) cells have gained increasing attention in adoptive cell therapy for their safety and efficacious tumor-killing effect. Unlike T cells which rely on the interaction between TCRs and specific peptide-MHC complexes, NK cells are more prone to be served as "off-the-shelf" cell therapy products due to their rapid recognition and killing of tumor cells without MHC restriction. In recent years, constantly emerging sources of therapeutic NK cells have provided flexible options for cancer immunotherapy. Advanced genetic engineering techniques, especially chimeric antigen receptor (CAR) modification, have yielded exciting effectiveness in enhancing NK cell specificity and cytotoxicity, improving in vivo persistence, and overcoming immunosuppressive factors derived from tumors. In this review, we highlight current advances in NK-based adoptive cell therapy, including alternative sources of NK cells for adoptive infusion, various CAR modifications that confer different targeting specificity to NK cells, multiple genetic engineering strategies to enhance NK cell function, as well as the latest clinical research on adoptive NK cell therapy.