Chimeric Antigen Receptor Natural Killer (CAR-NK)
CAR-NK (Chimeric Antigen Receptor Natural Killer) Cells: Overview and Therapeutic Potential
What are CAR-NK Cells?
Chimeric Antigen Receptor Natural Killer (CAR-NK) cells are genetically engineered natural killer (NK) cells that have been modified to express chimeric antigen receptors (CARs). These CARs enable NK cells to specifically recognize and target cancer cells expressing particular tumor-associated antigens. Unlike traditional T cells, CAR-NK cells do not require antigen priming and can recognize target cells independently of human leukocyte antigen (HLA) matching.
Mechanism and Advantages
- CAR-NK cells combine the innate killing ability of NK cells with the precise targeting ability afforded by CAR technology.
- They exert potent cytotoxic effects through secretion of perforin and granzyme, inducing apoptosis in cancer cells.
- CAR-NK therapy is associated with a lower risk of adverse effects such as cytokine release syndrome (CRS), neurotoxicity, and graft-versus-host disease (GvHD) compared to CAR-T cell therapy.
- The “off-the-shelf” nature of CAR-NK cells makes them more accessible as an immunotherapy option without the need for patient-specific customization.
- They also release immune-stimulating cytokines such as IFN-γ and TNF-α, enhancing the anti-tumor immune response.
Clinical Applications and Challenges
CAR-NK cell therapy is an emerging immunotherapy mainly investigated for hematologic malignancies such as leukemia and lymphoma and is being explored for solid tumors. While promising, challenges include overcoming the immunosuppressive tumor microenvironment and improving persistence and expansion of infused CAR-NK cells in patients.
Key Points
- CAR-NK cells are genetically engineered NK cells with enhanced specificity for cancer antigens.
- They offer potent anticancer effects with reduced side effects compared to CAR-T therapy.
- Their off-the-shelf availability offers advantages in manufacturing and clinical accessibility.
- Ongoing research focuses on tackling tumor immune evasion and improving therapeutic efficacy.
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References:
Balkhi S, dos Reis FD. CAR-NK cell therapy: promise and challenges in solid tumors. Front Immunol. 2025 Apr 6;16:1574742. doi:10.3389/fimmu.2025.1574742. Available at: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1574742/full
