Alloreactivity of ex vivo-expanded T cells is correlated with expansion and CD4/CD8 ratio

Cytotherapy
Patricia Mercier-LetondalEric Robinet

Abstract

Background We have demonstrated previously that retroviral-mediated transfer of a suicide gene into bone marrow (BM) donor T cells allows an efficient control of graft-versus-host disease (GvHD) after allogeneic BM transplantation. However, the 12 days of ex vivo culture required for the production of gene-modified cells (GMC), including soluble CD3 monoclonal antibody (MAb)-mediated activation and expansion with interleukin (IL)-2, induced a decrease of GMC alloreactivity and a reversal of their CD4/CD8 ratio. Improving the culture protocol in order to maintain the highest alloreactivity is of critical importance in obtaining an optimal graft-versus-leukemia (GvL) effect. Methods Peripheral blood mononuclear cells were activated with soluble CD3 MAb or CD3 and CD28 MAb co-immobilized on beads and expanded for 12 days in the presence of IL-2, IL-7 or IL-15 before analysis of alloreactivity and phenotype. Results Replacing the CD3 MAb by CD3/CD28 beads led to similar in vitro alloreactivity but improved the expansion and in vivo alloreactivity of GMC. Replacing the IL-2 with IL-7, but not IL-15, or decreasing IL-2 or IL-7 concentrations, improved the in vitro alloreactivity of expanded cells but was associated with lower expansi...Continue Reading

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Citations

Jan 22, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Céline LeboeufEric Robinet
Jun 10, 2019·Cancer Immunology, Immunotherapy : CII·Wenjie GongLeopold Sellner
Apr 28, 2017·Annals of Hematology·Holger BuddeTobias J Legler

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