Role of NK Cells in Cancer and Immunotherapy

Abstract

Increasing knowledge of cancer immunology has led to the design of therapies using immune cells directly or manipulating their activity, collectively termed immunotherapy. In the field of immuno-oncology, research on adaptive immune T cells has led to the development of CAR-T cells. Innate immune cells such as NK cells can also eliminate oncogenically transformed cells and regulate cells of the immune system. Considering NK cells as a live drug, numerous methods for the isolation and activation of NK cells have been shown to be clinically and therapeutically relevant. In such processes, various cytokines and antibodies present a source of stimulation of NK cells and enhance the efficacy of such treatments. The ex vivo expansion and activation of NK cells, along with genetic modification with CAR, enhance their antitumor activity. Recent preclinical studies have shown an antitumor effect through extracellular vesicles (EVs) derived from NK cells. Work with autologous NK cells has provided insights for clinical applications. In this review, we outline the recent advances of NK-cell-based immunotherapies, summarizing CAR-NK cells, BiKEs, and TriKEs as treatment options against cancer. This review also discusses the challenges of NK cell immunotherapy.

Natural Killer Cells and Cytotoxic T Cells: Complementary Partners against Microorganisms and Cancer

“…The addition of CAR expression to existing NK-cell-activating receptors could enhance NK cells’ ability to eliminate targeted tumor cells, especially in solid tumors often resistant to NK-cell-mediated killing. BiKEs and TriKEs are bispecific and trispecific killer engagers that can further enhance cytotoxic killing and cytokine production [ 261 ]. In a very recent review, Maia et al described how genetic modifications can enhance NK cells’ tumor-targeting capability, cytotoxicity, persistence, and tumor infiltration, and also prevent exhaustion, as well as detailed both non-viral (electroporation, lipid nanoparticles, lipofection, DNA transposons) and viral (lentivirus, gamma retrovirus, adeno-associated virus) technologies for genetically modifying NK cells [ 262 ].…”

Advances in natural killer cell therapies for breast cancer

“…4,10 A growing understanding of cancer immunology has led to the development of immunotherapy-the use of immune cells directly or by manipulation of their activity -as a therapeutic approach. 11 By activating immune responses, immunotherapies are designed to initiate an active or passive antitumor response against cancer. 12,13 A famous branch of cancer immunotherapy is adoptive cell therapy, in which immune cells are reprogrammed to attack tumor cells with greater precision than conventional chemo/radiation therapy and surgery.…”

“…18 Cancerous cells can be indirectly eliminated by NK cells via influencing immune system cells. 11 To distinguish between normal and malignant cells, NK cells have developed a variety of inherent strategies. It is noteworthy that the destruction of tumor cells by NK cell is independent of major histocompatibility complex I (MHC) molecules and antibodies.…”

“…A growing understanding of cancer immunology has led to the development of immunotherapy—the use of immune cells directly or by manipulation of their activity—as a therapeutic approach 11 . By activating immune responses, immunotherapies are designed to initiate an active or passive antitumor response against cancer 12,13 .…”

“…NK cells are cytotoxic innate lymphocytes capable of lysing malignant or virally contaminated cells 18 . Cancerous cells can be indirectly eliminated by NK cells via influencing immune system cells 11 . To distinguish between normal and malignant cells, NK cells have developed a variety of inherent strategies.…”