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by claude@2026-06, 2026-06-24
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The study engineered a chimeric antigen receptor platform (CARFcR) that incorporates an Fc receptor (CD16V158) so CAR-T cells can be activated either by CAR-mediated antigen recognition or by antibody-dependent recognition. Using human CARFcR-T cells, the authors report robust cytokine secretion, degranulation, and proliferation, with anti-CD19 CARFcR-T cells showing cytotoxicity comparable to conventional CAR-T cells and eliminating CD19+ leukemia in xenograft models, while also killing CD19-negative cells when guided by approved antibodies such as trastuzumab and rituximab. They further show that dual engagement enhances cytotoxicity and can eliminate CD19-negative escape variants, and that the same modular design extends to additional CAR targets (BCMA, CD123, CD33) with preserved function. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
ABSTRACT Chimeric antigen receptor (CAR)-T cell therapies achieve remarkable responses in hematologic malignancies but are limited by target heterogeneity and antigen escape; therapeutic antibodies offer flexible targeting yet cannot leverage T-cell effector function. Integrating CAR-T cell potency with antibody targeting adaptability could expand the clinical reach of cellular immunotherapy. We engineered a CAR platform (termed CAR FcR ) incorporating an Fc receptor (CD16 V158 ) into the CAR extracellular domain, and enabling both CAR-mediated targeting and antibody-dependent recognition. CAR FcR -T cells were activated through either pathway, exhibiting robust cytokine secretion, degranulation, and proliferation. Anti-CD19 CAR FcR -T cells mediated cytotoxicity comparable to conventional CAR-T cells and eradicated CD19 + leukemia in xenograft models. Importantly, they also exerted antibody-dependent killing of CD19-negative tumor cells when guided by clinically approved antibodies, such as anti-HER2 trastuzumab and anti-CD20 rituximab. Dual engagement further enhanced cytotoxicity and enabled elimination of CD19-negative escape variants. This modular CAR FcR architecture was successfully applied to additional CAR targets, including BCMA, CD123, and CD33, maintaining CAR function while allowing redirection with antibodies or CD16-binding bispecific engagers. Overall, CAR FcR represents a versatile and clinically adaptable platform that integrates the strengths of CAR-T cells and antibody therapeutics to expand tumor targeting and overcome antigen escape.
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ABSTRACT
Chimeric antigen receptor (CAR)-T cell therapies achieve remarkable responses in hematologic malignancies but are limited by target heterogeneity and antigen escape; therapeutic antibodies offer flexible targeting yet cannot leverage T-cell effector function. Integrating CAR-T cell potency with antibody targeting adaptability could expand the clinical reach of cellular immunotherapy. We engineered a CAR platform (termed CARFcR) incorporating an Fc receptor (CD16V158) into the CAR extracellular domain, and enabling both CAR-mediated targeting and antibody-dependent recognition. CARFcR-T cells were activated through either pathway, exhibiting robust cytokine secretion, degranulation, and proliferation. Anti-CD19 CARFcR-T cells mediated cytotoxicity comparable to conventional CAR-T cells and eradicated CD19+ leukemia in xenograft models. Importantly, they also exerted antibody-dependent killing of CD19-negative tumor cells when guided by clinically approved antibodies, such as anti-HER2 trastuzumab and anti-CD20 rituximab. Dual engagement further enhanced cytotoxicity and enabled elimination of CD19-negative escape variants. This modular CARFcR architecture was successfully applied to additional CAR targets, including BCMA, CD123, and CD33, maintaining CAR function while allowing redirection with antibodies or CD16-binding bispecific engagers. Overall, CARFcR represents a versatile and clinically adaptable platform that integrates the strengths of CAR-T cells and antibody therapeutics to expand tumor targeting and overcome antigen escape.
Competing Interest Statement
N.V. and D.C. are listed as inventors in a patent application describing the CARFcR technology, and hold other patents related to CAR-T cell therapy. D.C. is scientific founder and stockholder of Nkarta Therapeutics and Medisix Therapeutics. J.Y and N.A.N.H. declare no competing interests.
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