Anticancer traits of chimeric antigen receptors (CARs)-Natural Killer (NK) cells as novel approaches for melanoma treatment

Abstract

Owing to non-responsiveness of a high number of patients to the common melanoma therapies, seeking novel approaches seem as an unmet requirement. Chimeric antigen receptor (CAR) T cells were initially employed against recurrent or refractory B cell malignancies. However, advanced stages or pretreated patients have insufficient T cells (lymphopenia) amount for collection and clinical application. Additionally, this process is time-consuming and logistically cumbersome. Another limitation of this approach is toxicity and cytokine release syndrome (CRS) progress and neurotoxicity syndrome (NS). Natural killer (NK) cells are a versatile component of the innate immunity and have several advantages over T cells in the application for therapies such as availability, unique biological features, safety profile, cost effectiveness and higher tissue residence. Additionally, CAR NK cells do not develop Graft-versus-host disease (GvHD) and are independent of host HLA genotype. Notably, the NK cells number and activity is affected in the tumor microenvironment (TME), paving the way for developing novel approaches by enhancing their maturation and functionality. The CAR NK cells short lifespan is a double edge sword declining toxicity and reducing their persistence. Bispecific and Trispecific Killer Cell Engagers (BiKE and Trike, respectively) are emerging and promising immunotherapies for efficient antibody dependent cell cytotoxicity (ADCC). CAR NK cells have some limitations in terms of expanding and transducing NK cells from donors to achieve clinical response. Clinical trials are in scarcity regarding the CAR NK cell-based cancer therapies. The CAR NK cells short life span following irradiation before infusion limits their efficiency inhibiting their in vivo expansion. The CAR NK cells efficacy enhancement in terms of lifespan TME preparation and stability is a goal for melanoma treatment. Combination therapies using CAR NK cells and chemotherapy can also overcome therapy limitations.

Advances in Bacterial Lysate Immunotherapy for Infectious Diseases and Cancer

“…In cancer immunology, activating and stimulating NK cells and M φ using bacterial products or PRRs agonists have indicated the ability to correct immunosuppressive tumor microenvironment inadequacies [ 126 ]. Classical activation of M φ , which is associated with high IL-12 and low IL-10, by bacterial products may offset the protumor effects of tumor-associated M φ , which has low IL-12 and elevated IL-10 [ 127 , 128 ].…”

The role of tumor-infiltrating lymphocytes in triple-negative breast cancer and the research progress of adoptive cell therapy

“…NK cells are mainly derived from peripheral blood, umbilical cord blood, stem cells, and NK92 cell lines. CAR-NK cell models are obtained by using viral or non-viral vectors to transduce CARs into NK cells ( 60 ).…”

Cellular Therapies in Chronic Lymphocytic Leukemia and Richter’s Transformation: Recent Developments in Chimeric Antigen Receptor T-Cells, Natural Killer Cells, and Allogeneic Stem Cell Transplant

“…Some clinical trials are evaluating CAR NK in both solid tumors and lymphomas, whereas others focus on a single cancer type such as melanoma [ 104 ]. FT500 is an iPSC-derived NK cell therapy.…”