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- W1541573460 abstract "Abstract A new strategy to improve the therapeutic utility of redirected T cells for cancer involves the development of novel Ag-specific chimeric receptors capable of stimulating optimal and sustained T cell antitumor activity in vivo. Given that T cells require both primary and costimulatory signals for optimal activation and that many tumors do not express critical costimulatory ligands, modified single-chain Ab receptors have been engineered to codeliver CD28 costimulation. In this study, we have compared the antitumor potency of primary T lymphocytes expressing carcinoembryonic Ag (CEA)-reactive chimeric receptors that incorporate either TCR-ζ or CD28/TCR-ζ signaling. Although both receptor-transduced T cell effector populations demonstrated cytolysis of CEA+ tumors in vitro, T cells expressing the single-chain variable fragment of Ig (scFv)-CD28-ζ chimera had a far greater capacity to control the growth of CEA+ xenogeneic and syngeneic colon carcinomas in vivo. The observed enhanced antitumor activity of T cells expressing the scFv-CD28-ζ receptor was critically dependent on perforin and the production of IFN-γ. Overall, this study has illustrated the ability of a chimeric scFv receptor capable of harnessing the signaling machinery of both TCR-ζ and CD28 to augment T cell immunity against tumors that have lost expression of both MHC/peptide and costimulatory ligands in vivo." @default.
- W1541573460 created "2016-06-24" @default.
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- W1541573460 date "2002-11-15" @default.
- W1541573460 modified "2023-10-10" @default.
- W1541573460 title "Rejection of Syngeneic Colon Carcinoma by CTLs Expressing Single-Chain Antibody Receptors Codelivering CD28 Costimulation" @default.
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- W1541573460 doi "https://doi.org/10.4049/jimmunol.169.10.5780" @default.
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