Influence of Retronectin-Mediated T-Cell Activation on Expansion and Phenotype of CD19-Specific Chimeric Antigen Receptor T Cells

Human Gene Therapy
Sophia StockLeopold Sellner

Abstract

Enhanced in vivo expansion, long-term persistence of chimeric antigen receptor T (CART) cells, and efficient tumor eradication through these cells are linked to the proportion of less-differentiated cells in the CART cell product. Retronectin is well established as an adjuvant for improved retroviral transduction, while its property to enrich less-differentiated T cells is less known. In order to increase these subsets, this study investigated the effects of retronectin-mediated T-cell activation for CD19-specific CART cell production. Peripheral blood mononuclear cells of healthy donors and untreated chronic lymphocytic leukemia (CLL) patients without or with positive selection for CD3+ T cells were transduced with a CD19.CAR.CD28.CD137zeta third-generation retroviral vector. Activation of peripheral blood mononuclear cells was performed by CD3/CD28, CD3/CD28/retronectin, or CD3/retronectin. Interleukin-7 and -15 were supplemented to all cultures. Retronectin was used in all three activation protocols for retroviral transduction. Expansion was assessed by trypan blue staining. Viability, transduction efficiency, immune phenotype, and cytokine production were longitudinally analyzed by flow cytometry. Cytotoxic capacity of gene...Continue Reading

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Citations

Feb 10, 2019·International Journal of Cancer. Journal International Du Cancer·Sophia StockLeopold Sellner
Jun 10, 2019·Cancer Immunology, Immunotherapy : CII·Wenjie GongLeopold Sellner
Apr 10, 2020·International Journal of Cancer. Journal International Du Cancer·Leopold SellnerMichael Schmitt
Jul 20, 2020·International Journal of Cancer. Journal International Du Cancer·Fuli FanLeopold Sellner
May 22, 2019·International Journal of Molecular Sciences·Hyeon Joo YooLeopold Sellner
Dec 15, 2019·International Journal of Molecular Sciences·Sophia StockLeopold Sellner
Jun 15, 2021·Frontiers in Immunology·Mingya YangAnita Schmitt
May 24, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yohei KawaiShin Kaneko

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Methods Mentioned

BETA
transfection
FACS

Software Mentioned

GraphPad Prism
Excel
Word
FlowJo
GraphPad

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