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• W2097320461 abstract "In spite of increased rates of complete response to initial chemotherapy, most patients with advanced ovarian cancer relapse and succumb to progressive disease.Genetically reprogrammed, patient-derived chimeric antigen receptor (CAR)-T lymphocytes with the ability to recognize predefined surface antigens with high specificity in a non-MHC restricted manner have shown increasing anti-tumor efficacy in preclinical and clinical studies. Folate receptor-α (FRα) is an ovarian cancer-specific tumor target; however, it is expressed at low levels in certain organs with risk for toxicity.Here we propose a phase I study testing the feasibility, safety and preliminary activity of FRα-redirected CAR-T cells bearing the CD137 (4-1BB) costimulatory domain, administered after lymphodepletion for the treatment of recurrent ovarian cancer. A novel trial design is proposed that maximizes safety features.This design involves an initial accelerated dose escalation phase of FR-α CAR-T cells followed by a standard 3 + 3 escalation phase. A split-dose approach is proposed to mitigate acute adverse events. Furthermore, infusion of bulk untransduced autologous peripheral blood lymphocytes (PBL) is proposed two days after CAR-T cell infusion at the lower dose levels of CAR-T cells, to suppress excessive expansion of CAR-T cells in vivo and mitigate toxicity." @default.
• W2097320461 created "2016-06-24" @default.
• W2097320461 creator A5007749781 @default.
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• W2097320461 date "2012-08-03" @default.
• W2097320461 modified "2023-09-27" @default.
• W2097320461 title "A phase I clinical trial of adoptive transfer of folate receptor-alpha redirected autologous T cells for recurrent ovarian cancer" @default.
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• W2097320461 doi "https://doi.org/10.1186/1479-5876-10-157" @default.
• W2097320461 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3439340" @default.
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