ArticleCancer immunology, immunotherapy : CII2026
Human CD3 complex is required for the generation of T-cell receptor-like chimeric antigen receptor targeting WT1 in natural killer cells.
Article in Cancer immunology, immunotherapy : CII, 2026. 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
Chimeric antigen receptor-natural killer (CAR-NK) cells represent a promising cellular immunotherapy platform for various cancers, offering a favorable clinical safety profile and potential to generate off-the-shelf products. However, broader application of CAR-NK cells is in part restricted by the availability of surface tumor antigens. T-cell receptor (TCR)-like CARs have gained increasing attention due to their ability to recognize peptides derived from intracellular tumor antigens presented by major histocompatibility complex molecules. In the present study, we designed a third-generation CAR targeting WT1(126-134) peptide presented by HLA-A*02:01, harboring a TCR-like scFv linked to CD28, 4-1BB, and CD3ζ signaling domains (CAR-WT1), and introduced it into human NK-92 cells-the only FDA-approved NK cell line for clinical trials. Interestingly, we found that surface expression of CAR-WT1 in NK-92 cells required the presence of human CD3 complex, as observed for full-length TCRs. Quantitative PCR and subsequent pathway and network analyses indicated enhanced immune activation potentially relevant to effector function in CAR-WT1/CD3 NK-92 cells. The established CAR-WT1/CD3 NK-92 cells exhibited significantly greater cytotoxicity against WT1
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