A phase I clinical trial of adoptive transfer of folate receptor-alpha redirected autologous T cells for recurrent ovarian cancer.

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Serval ID
serval:BIB_695ACE74094E
Type
Article: article from journal or magazin.
Collection
Publications
Title
A phase I clinical trial of adoptive transfer of folate receptor-alpha redirected autologous T cells for recurrent ovarian cancer.
Journal
Journal of Translational Medicine
Author(s)
Kandalaft L.E., Powell D.J., Coukos G.
ISSN
1479-5876 (Electronic)
ISSN-L
1479-5876
Publication state
Published
Issued date
2012
Volume
10
Pages
157
Language
english
Notes
Publication types: Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't Publication Status: epublish
Abstract
PURPOSE: In spite of increased rates of complete response to initial chemotherapy, most patients with advanced ovarian cancer relapse and succumb to progressive disease.
RATIONALE: 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.
DESIGN: 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.
INNOVATION: 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.
Keywords
Adoptive Transfer, Feasibility Studies, Female, Folate Receptor 1/immunology, Humans, Ovarian Neoplasms/metabolism, Ovarian Neoplasms/pathology, Recurrence, T-Lymphocytes/immunology
Pubmed
Web of science
Open Access
Yes
Create date
14/10/2014 11:42
Last modification date
20/08/2019 14:24
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