Premium
Uncoupling T‐cell expansion from effector differentiation in cell‐based immunotherapy
Author(s) -
Crompton Joseph G.,
Sukumar Madhusudhanan,
Restifo Nicholas P.
Publication year - 2014
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12135
Subject(s) - effector , biology , adoptive cell transfer , cytolysis , cd8 , cell therapy , immunotherapy , immunology , cellular differentiation , cytotoxic t cell , microbiology and biotechnology , phenotype , cancer immunotherapy , cancer research , t cell , immune system , stem cell , in vitro , genetics , gene
Summary Adoptive cellular immunotherapy ( ACT ) is a potentially curative therapy for patients with advanced cancer. Eradication of tumor in mouse models and humans correlates with both a high dose of adoptively transferred cells and cells with a minimally differentiated phenotype that maintain replicative capacity and multipotency. We speculate that response to ACT not only requires transfer of cells with immediate cytolytic effector function to kill the bulk of fast‐growing tumor but also transfer of tumor‐specific cells that maintain an ability for self‐renewal and the capacity to produce a continual supply of cytolytic effector progeny until all malignant cells are eliminated. Current in vitro methods to expand cells to sufficient numbers and still maintain a minimally differentiated phenotype are hindered by the biological coupling of clonal expansion and effector differentiation. Therefore, a better understanding of the physiologic mechanism that couples cell expansion and differentiation in CD 8 + T cells may improve the efficacy of ACT .