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

Successful adoptive T-cell therapy has been demonstrated in viral disease(1 ,2) and selected forms of cancer(3). However, it is limited by the difficul ty to efficiently isolate and amplify autologous tumor-reactive T-cell clon es. Tetramers of major histocompatibility complex (MHC) class I and peptide have facilitated the characterization of CD8(+) T cells specific for tumor -associated antigens(4,5). However, for adoptive T-cell therapy, MHC-tetram ers have limitations: they require knowledge of tumor antigens, which is of ten not available; they select T cells with a single specificity, thereby p osing risk for selection of tumor escape variants; they do not select for f unction, 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 essentia l for tumor rejection(6). Because interferon (IFN)-gamma is essential for t umor rejection(7,8), we isolated live T cells based on their IFN-gamma prod uction(9). IFN-gamma secreted by previously activated T cells is retained o n the cell surface, allowing their specific isolation and expansion(10). We show here that IFN-gamma (+) but not IFN-gamma (-) T cells from tumor-immu nized mice are cytolytic and mediate tumor rejection upon adoptive transfer . Importantly, tumor-specific T cells can be enriched from lymphocytes infi ltrating human renal cell carcinoma by the IFN-gamma capture assay.