Emerging Frontiers in Cancer Immunotherapy: Recent Advances in CAR-NK Cell and CAR-Macrophage Therapies
DOI:
https://doi.org/10.61173/j0vz8336Keywords:
CAR-NK cells, CAR-macrophages, cancer immunotherapy, tumor microenvironment (TME)Abstract
Chimeric antigen receptor (CAR) cell therapies have revolutionized the field of cancer treatment with the breakthrough successes of CAR-T cell therapy in hematological malignancies. However, CAR-T cell efficacy in solid tumors has been limited by challenges such as the immunosuppressive tumor microenvironment (TME) and safety concerns like cytokine release syndrome (CRS) and graft-versus-host disease (GvHD). This review focuses on the latest advancements in CAR-NK cell and CAR-macrophage therapies, which offer potential solutions to these limitations. CAR-NK cells exhibit natural cytotoxicity and MHC-independent tumor targeting, providing a safer profile with lower risks of GvHD and CRS compared to CAR-T cells. Innovations in CAR-NK cell therapy includes structural optimizations, gene editing with CRISPR-Cas9, and the development of multispecific CARs, all contributing to enhanced anti-tumor efficacy, especially in solid tumors. Meanwhile, CAR-macrophages are effective in remodeling the TME through phagocytosis and immune activation, addressing the challenges of solid tumor infiltration. This review compares the mechanisms of action, clinical applications, and safety profiles of CAR-NK cells and CAR-macrophages, highlighting the synergistic potential of these therapies. Although clinical research on both therapies is still in its early stages, the promising preclinical and early clinical trial results underscore their potential as alternative immunotherapies for refractory cancers. Future research will focus on overcoming challenges in production scalability, improving in vivo persistence, and personalizing CAR therapies through precision medicine approaches. These two therapies will likely play pivotal roles in the next generation of cancer immunotherapies.
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