Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products

Journal of Immunotherapy
Theodore S NowickiBegoña Comin-Anduix

Abstract

Adoptive cell therapy (ACT) consisting of genetically engineered T cells expressing tumor antigen-specific T-cell receptors displays robust initial antitumor activity, followed by loss of T-cell activity/persistence and frequent disease relapse. We characterized baseline and longitudinal T-cell phenotype variations resulting from different manufacturing and administration protocols in patients who received ACT. Patients with melanoma who enrolled in the F5-MART-1 clinical trial (NCT00910650) received infusions of MART-1 T-cell receptors transgenic T cells with MART-1 peptide-pulsed dendritic cell vaccination. Patients were divided into cohorts based on several manufacturing changes in the generation and administration of the transgenic T cells: decreasing ex vivo stimulation/expansion time, increased cell dose, and receiving fresh instead of cryopreserved cells. T-cell phenotypes were analyzed by flow cytometry at baseline and longitudinally in peripheral blood. Transgenic T cells with shorter ex vivo culture/expansion periods displayed significantly increased expression of markers associated with less differentiated naive/memory populations, as well as significantly decreased expression of the inhibitory receptor programmed de...Continue Reading

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Citations

Aug 10, 2020·Nature Communications·Julia BoshuizenDaniel S Peeper
Dec 24, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Theodore S NowickiAntoni Ribas

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Methods Mentioned

BETA
transgenic
biopsies
biopsy
flow cytometry

Clinical Trials Mentioned

NCT00910650

Software Mentioned

FlowJo
GraphPad Prism
Cytobank

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