Adoptive tumor therapy with T lymphocytes enriched through an IFN-gamma capture assay.
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-gamma 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.
Becker
C
C
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Pohla
H
H
Frankenberger
B
B
Schüler
T
T
Assenmacher
M
M
Schendel
D J
DJ
Blankenstein
T
T
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000628:therapy; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D007371:Interferon-gamma