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• W2058219351 abstract "Abstract Purpose: The purpose of the present study was to evaluate the capacity and mechanisms of genetically modified erbB2-specific T cells to eradicate erbB2+ tumors in syngeneic mice. Experimental Design: Primary mouse T cells were modified to target the breast tumor–associated antigen erbB2 through retroviral-mediated transfer of a chimeric antigen receptor, termed single-chain antibody (scFv)–CD28–ζ. Antitumor efficacy of scFv-CD28-ζ–modified T cells was analyzed in mice bearing D2F2/E2 breast tumors. Results: The scFv-CD28-ζ–modified T cells were shown to specifically secrete T cytotoxic-1 cytokines and lyse erbB2+ breast tumor cells following receptor stimulation in vitro. Treatment with scFv-CD28-ζ–modified T cells was able to lead to long-term, tumor-free survival in mice bearing erbB2+ D2F2/E2 breast tumors. Importantly, the surviving mice developed a host memory response to D2F2/E2 tumor cells, and this host response was able to protect against a rechallenge with erbB2+ D2F2/E2 tumor cells and parental erbB2- D2F2 tumor cells. In addition, scFv-CD28-ζ T-cell expression of perforin and interferon-γ were essential for complete antitumor efficacy. Conclusions: Treatment with scFv-CD28-ζ–modified T cells was able to induce a host antitumor immunity in syngeneic mice. Complete tumor elimination by scFv-CD28-ζ–modified T cells required T cell–derived interferon-γ and perforin, indicating that cytotoxicity and cytokine secretion play a role in the in vivo response." @default.
• W2058219351 created "2016-06-24" @default.
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• W2058219351 date "2009-02-01" @default.
• W2058219351 modified "2023-09-26" @default.
• W2058219351 title "Genetically Targeted T Cells Eradicate Established Breast Cancer in Syngeneic Mice" @default.
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• W2058219351 doi "https://doi.org/10.1158/1078-0432.ccr-08-2381" @default.
• W2058219351 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19188165" @default.
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