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TOP CAR with TMIGD2 as a safe and effective costimulatory domain in CAR cells treating human solid tumors

Sci Adv. 2024-05; 
Christopher D Nishimura, Devin Corrigan, Xiang Yu Zheng, Phillip M Galbo, Shan Wang, Yao Liu, Yao Wei, Linna Suo, Wei Cui, Nadia Mercado, Deyou Zheng, Cheng Cheng Zhang, Xingxing Zang
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Proteins, Expression, Isolation and Analysis … Next, the proteins were separated via SDS-PAGE gel electrophoresis (GenScript, Nanjing, China). In this study, the protein was transferred from SDS-PAGE gel to polyvinylidene … Get A Quote

摘要

Chimeric antigen receptor (CAR)-T cell therapy shows impressive efficacy treating hematologic malignancies but requires further optimization in solid tumors. Here, we developed a TMIGD2 optimized potent/persistent (TOP) CAR that incorporated the costimulatory domain of TMIGD2, a T and NK cell costimulator, and monoclonal antibodies targeting the IgV domain of B7-H3, an immune checkpoint expressed on solid tumors and tumor vasculature. Comparing second- and third-generation B7-H3 CARs containing TMIGD2, CD28, and/or 4-1BB costimulatory domains revealed superior antitumor responses in B7-H3.TMIGD2 and B7-H3.CD28.4-1BB CAR-T cells in vitro. Comparing these two constructs using in vivo orthotopic human cancer model... More

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