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G36-CD28-TCRζ CAR-T cells are an investigational, fully human, second-generation chimeric antigen receptor (CAR) T-cell therapy developed by the Dana-Farber Cancer Institute for the treatment of renal cell carcinoma (RCC). The therapy targets Carbonic Anhydrase IX (CAIX), a tumor-associated antigen overexpressed in over 90% of clear-cell RCC but with limited expression in normal tissues. The CAR construct utilizes the human G36 single-chain variable fragment (scFv) for antigen recognition, linked to a CD28 co-stimulatory domain and a T-cell receptor zeta chain (TCRζ) signaling domain for T-cell activation. Preclinical studies in mouse models have demonstrated that this therapy, especially when combined with high-dose interleukin-2, leads to significant tumor regression, apoptosis, and tissue necrosis. The fully human design is intended to minimize immunogenicity and human anti-mouse antibody (HAMA) responses, potentially allowing for lower T-cell doses in clinical applications.
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