NK Cell‐Based Cancer Immunotherapies: Current Progress, Challenges and Emerging Opportunities

• Published in: Journal of biochemical and molecular toxicology Vol. 38; no. 11; pp. e70044 - n/a
• Main Authors: Alshahrani, Mohammad Y., Uthirapathy, Subasini, Kumar, Abhinav, Oghenemaro, Enwa Felix, R., Roopashree, Lal, Madan, Arora, Isha, Chauhan, Ashish Singh, Saud, Mahmood Jumaa, Hulail, Hanen Mahmod
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2024
• Subjects: adoptive cell transplantation; Allografts; Animals; Anticancer properties; Antitumor activity; Cancer; Cancer immunotherapy; Cancer therapies; CAR NK cell; Cell therapy; combination therapy; drug resistance; Exosomes; Exosomes - immunology; Exosomes - transplantation; Humans; Immune system; Immunology; Immunosuppressive agents; Immunotherapy; Immunotherapy - methods; Killer Cells, Natural - immunology; Monoclonal antibodies; Natural killer cells; Neoplasms - immunology; Neoplasms - therapy; Side effects; Therapy; Tumor microenvironment; Tumor Microenvironment - immunology; Tumors; combination therapy; drug resistance; tumor microenvironment; adoptive cell transplantation; CAR NK cell; exosomes
• ISSN: 1095-6670; 1099-0461; 1099-0461
• DOI: 10.1002/jbt.70044

ABSTRACT Natural killer (NK) cells are vital innate immune cells that play a crucial role in cancer therapy. They are targeted by therapies designed to modulate, retain, and enhance their antitumor function in vivo. In addition to whole‐cell therapy, NK cell‐derived exosomes (NDEs) offer high immune safety and are easily subject to chemical, biological, and immunological modifications. This makes them suitable for use in combination with various current cancer therapies to enhance efficacy, treatment outcomes, and reduce side effects in vivo. This review aims to outline summarizes the antitumor potential of NK cells, as well as the current challenges and opportunities in NK cell‐based immunotherapies such as allogeneic and autologous NK cell transplantation, CAR NK cell therapy, and the use of cytokines and monoclonal antibodies. The review also explores the dual regulatory effects of tumor exosomes on NK cells, and highlights the potential of NDEs, either alone or in combination with other antitumor therapies, to reprogram the immunosuppressive tumor microenvironment and expedite the therapeutic effects of cancer immunotherapy in future clinical research. Approaches to NK cell cancer immunotherapies include: therapy‐mediated NK cell recruitment and activation using cytokines/chemokines, transfusions of genetically modified CAR NK cells, and administration of monoclonal antibodies against checkpoint molecules, activatory/inhibitory receptors, or mAb to induce ADCC by engaging CD16 and tumor‐specific antigen. Interestingly, NK cell‐derived exosomes have potential in immune responses for cancer immunotherapy.