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• W3198344470 abstract "Engineered T cells that express chimeric antigen receptors (CARs) have been a promising therapy for hematologic malignancies. The optimization of CAR structure using different signaling domains can alter a wide range of CAR-T cell properties, including anti-tumor activity, long-term persistence, and safety. In this study, we developed a novel CAR structure based on KIRS2/Dap12 for B cell acute lymphoblastic leukemia (B-ALL) antigen CD19 and compared the anti-tumor efficacy and safety of this construct in transduced T cells with standard second-generation CAR-T cells targeting CD19 for B-ALL in vitro and in vivo and in adult relapsed/refractory (r/r) B-ALL patients. We discovered that KIRS2/Dap12 receptor infused with 4-1BB co-stimulation domain could enhance anti-tumor efficacy by remarkably increasing the production of pro-inflammatory interleukin-2 (IL-2), especially when co-cultured with antigen-positive tumor cells. In addition, CD19-KIRS2/Dap12-BB CAR-T cells showed the inspiring outcome that complete responses were seen in 4 of 4 (100%) patients without neurotoxicity and a high rate of severe cytokine release syndrome (CRS) after CAR-T infusion in a phase I clinical trial. Given these encouraging findings, CD19-KIRS2/Dap12-BB CAR-T cells are safe and can lead to clinical responses in adult patients with r/r B-ALL, indicating that further assessment of this therapy is warranted." @default.
• W3198344470 created "2021-09-13" @default.
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• W3198344470 date "2021-12-01" @default.
• W3198344470 modified "2023-10-14" @default.
• W3198344470 title "Novel two-chain structure utilizing KIRS2/DAP12 domain improves the safety and efficacy of CAR-T cells in adults with r/r B-ALL" @default.
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• W3198344470 doi "https://doi.org/10.1016/j.omto.2021.08.014" @default.
• W3198344470 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8517091" @default.
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