ArticleFrontiers in immunology2025
Construction of anti-HER2 affibody-directed CAR-NK and its synergistic effects with doxorubicin-loaded nanodrug against HER2-positive breast cancer.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Chimeric antigen receptor (CAR)-engineered T or natural killer (NK) cells are a promising approach for cancer immunotherapy. The leading region of the CAR structure is generally a single-chain antibody (scFv) fragment specific for a tumor cell surface molecule, and other structures are rarely reported. Methods: In this study, we developed a novel anti-human epidermal growth factor receptor 2 (HER2) CAR-NK cell using an affibody molecule as the extracellular targeting domain instead of a conventional scFv. Affibody-based CAR-NK cells were generated from the NK-92 cell line. To enhance safety, CAR-NK cells were subjected to γ-irradiation, and their antitumor activity was further evaluated in combination with doxorubicin (DOX)-loaded nanoparticles. Results: Affibody-based CAR-NK cells exhibited effective cytotoxicity against HER2-positive breast cancer cells, comparable to that of anti-HER2 scFv-based CAR-NK cells. γ-Irradiation at 10 Gy effectively inhibited malignant proliferation of CAR-NK cells but significantly reduced their cytotoxic activity. Notably, incorporation of DOX-loaded nanoparticles markedly enhanced the killing capacity of irradiated CAR-NK cells, restoring and even amplifying their antitumor efficacy. Discussion: These findings demonstrate that affibody-based CAR-NK cells are a viable alternative to conventional scFv-based CAR constructs. Moreover, the combination of CAR-NK immunotherapy with chemotherapeutic nanomedicine effectively compensates for irradiation-induced cytotoxicity attenuation, offering a promising synergistic strategy for the treatment of HER2-positive breast cancer.
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