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Adoptive tumor therapy with T lymphocytes enriched through an IFN-gamma capture assay

PubMed:View item in PubMed
Creators Name:Becker, C. and Pohla, H. and Frankenberger, B. and Schueler, T. and Assenmacher, M. and Schendel, D.J. and Blankenstein, T.
Journal Title:Nature Medicine
Journal Abbreviation:Nat Med
Volume:7
Number:10
Page Range:1159-1162
Date:1 January 2001
Keywords:Adoptive Immunotherapy, Colonic Neoplasms, Cultured Tumor Cells, Fibrosarcoma, Inbred BALB C Mice, Interferon Type II, Kidney Neoplasms, Neoplasms, Renal Cell Carcinoma, T-Lymphocytes, Animals, Mice
Abstract:Successful adoptive T-cell therapy has been demonstrated in viral disease and selected forms of cancer. However, it is limited by the difficulty to efficiently isolate and amplify autologous tumor-reactive T-cell clones. Tetramers of major histocompatibility complex (MHC) class I and peptide have facilitated the characterization of CD8 + T cells specific for tumor-associated antigens. However, for adoptive T-cell therapy, MHC-tetramers have limitations: they require knowledge of tumor antigens, which is often not available; they select T cells with a single specificity, thereby posing risk for selection of tumor escape variants; they do not select for function, so that T cells may be anergic when isolated from cancer patients; and they do not allow the isolation of CD4 + T cells that can be essential for tumor rejection. Because interferon (IFN)-{gamma} is essential for tumor rejection, we isolated live T cells based on their IFN-γ production. IFN-{gamma} secreted by previously activated T cells is retained on the cell surface, allowing their specific isolation and expansion. We show here that IFN-{gamma} but not IFN-{gamma} T cells from tumor-immunized mice are cytolytic and mediate tumor rejection upon adoptive transfer. Importantly, tumor-specific T cells can be enriched from lymphocytes infiltrating human renal cell carcinoma by the IFN-{gamma} capture assay.
ISSN:1078-8956
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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