| Bispecific T-cells Expressing Polyclonal Repertoire of Endogenous γδ T-cell Receptors and Introduced CD19-specific Chimeric Antigen Receptor. | |
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MedLine Citation:
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PMID: 23295945 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Even though other γδ T-cell subsets exhibit antitumor activity, adoptive transfer of γδ Tcells is currently limited to one subset (expressing Vγ9Vδ2 T-cell receptor (TCR)) due to dependence on aminobisphosphonates as the only clinically appealing reagent for propagating γδ T cells. Therefore, we developed an approach to propagate polyclonal γδ T cells and rendered them bispecific through expression of a CD19-specific chimeric antigen receptor (CAR). Peripheral blood mononuclear cells (PBMC) were electroporated with Sleeping Beauty (SB) transposon and transposase to enforce expression of CAR in multiple γδ T-cell subsets. CAR(+)γδ T cells were expanded on CD19(+) artificial antigen-presenting cells (aAPC), which resulted in >10(9) CAR(+)γδ T cells from <10(6) total cells. Digital multiplex assay detected TCR mRNA coding for Vδ1, Vδ2, and Vδ3 with Vγ2, Vγ7, Vγ8, Vγ9, and Vγ10 alleles. Polyclonal CAR(+)γδ T cells were functional when TCRγδ and CAR were stimulated and displayed enhanced killing of CD19(+) tumor cell lines compared with CAR(neg)γδ T cells. CD19(+) leukemia xenografts in mice were reduced with CAR(+)γδ T cells compared with control mice. Since CAR, SB, and aAPC have been adapted for human application, clinical trials can now focus on the therapeutic potential of polyclonal γδ T cells.Molecular Therapy (2013); doi:10.1038/mt.2012.267. |
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Authors:
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Drew C Deniger; Kirsten Switzer; Tiejuan Mi; Sourindra Maiti; Lenka Hurton; Harjeet Singh; Helen Huls; Simon Olivares; Dean A Lee; Richard E Champlin; Laurence Jn Cooper |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-08 |
Journal Detail:
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Title: Molecular therapy : the journal of the American Society of Gene Therapy Volume: - ISSN: 1525-0024 ISO Abbreviation: Mol. Ther. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100890581 Medline TA: Mol Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Division of Pediatrics, Children's Cancer Hospital, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA [2] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA. |
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