The Role of NK Cells in Cancer Immunotherapy: Mechanisms, Evasion Strategies, and Therapeutic Advances

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 857 - 857

Published: April 2, 2025

Background/Objectives: Natural killer (NK) cells play a crucial role in tumor surveillance by exerting cytotoxic activity and modulating immune responses. However, tumors employ diverse evasion strategies that limit NK cell effectiveness. This review aims to explore the molecular mechanisms of activation inhibition cancer, influence microenvironment, latest advancements cell-based immunotherapies, including adoptive transfer Chimeric Antigen Receptor-Natural Killer (CAR-NK) therapies. Methods: A comprehensive literature was conducted, prioritizing peer-reviewed studies from last decade on biology, evasion, immunotherapeutic applications. The analysis includes data preclinical models clinical trials evaluating expansion strategies, cytokine-based stimulation, CAR-NK therapy developments. Results: eliminate through granule release, death receptor pathways, cytokine secretion. evade NK-mediated immunity downregulating activating ligands, secreting immunosuppressive molecules, altering microenvironment. Novel therapies, such as combination approaches with checkpoint inhibitors, enhance persistence therapeutic efficacy against both hematologic solid malignancies. Clinical suggest improved safety profiles compared CAR-T reduced release syndrome graft-versus-host disease. Conclusions: While immunotherapies hold great promise, challenges remain, limited tumor-induced immunosuppression. Addressing these hurdles will be critical for optimizing therapies advancing next-generation, off-the-shelf immunotherapeutics broader

Language: Английский

Interleukin-21 engineering enhances CD19-specific CAR-NK cell activity against B-cell lymphoma via enriched metabolic pathways

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: April 2, 2025

Abstract Background NK cells engineered to express interleukin-15 (IL-15) and a CD19-targeted chimeric antigen receptor (CAR) have been used treat patients with relapsed and/or refractory B cell malignances, demonstrating encouraging outcomes favorable safety profile. However, the effect of IL-21 in CAR-NK therapy remains unknown. Methods CD19-specific CAR 4-1BB costimulatory domain cytokine or IL-15 was constructed transduced into peripheral blood (PB)-derived produce CD19-CAR-IL21 (CAR-21) CD19-CAR-IL15 (CAR-15), respectively. The phenotypic profile, transcriptomic characteristics, functionality anti-tumor activity CAR-21 CAR-15 were compared. Results Compared co-expressing IL-15, exhibited significantly increased IFN-γ, TNF-α Granzyme production, as well degranulation, response CD19 + Raji lymphoma cells, resulting enhanced cytotoxic upon repetitive tumor stimulation. Furthermore, co-expression improved vivo persistence suppressed growth xenograft murine model, leading prolonged survival tumor-bearing mice. RNA sequencing revealed that distinct signature characterized by enriched cytokine, cytotoxicity, metabolic related signaling, when compared cells. Conclusions This study demonstrated exhibit superior against which might be promising therapeutic strategy for treating relapse malignances.

Language: Английский

Emerging Role of Chimeric Antigen Receptor-Natural Killer Cells for the Treatment of Hematologic Malignancies

Cancers, Journal Year: 2025, Volume and Issue: 17(9), P. 1454 - 1454

Published: April 26, 2025

The clinical use of T lymphocytes engineered with chimeric antigen receptors (CARs) has revolutionized the treatment patients refractory or relapsed hematological malignancies. CAR natural killer (CAR-NK) cells are NK CARs to specifically target cell antigens expressed on membrane tumor cells. CAR-NK could offer some advantages respect CAR-T cells, related their specific and innate anti-tumor activity, availability as an “off shelf” cellular therapy, reduced costs, improved safety. Promising efficacy CAR-Nk therapy was observed in trials based However, date, experience been preliminary, evaluation only a limited number patients. Furthermore, by short persistence these suboptimal cytotoxic activity preparations. Therefore, studies enrollment is required carefully assess confirm safety malignancies compare allogeneic

Language: Английский