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

Abstract

Successful adoptive T-cell therapy has been demonstrated in viral disease^1,2 and selected forms of cancer³. 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^4,5. 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 rejection⁶. Because interferon (IFN)-γ is essential for tumor rejection^7,8, we isolated live T cells based on their IFN-γ production⁹. IFN-γ secreted by previously activated T cells is retained on the cell surface, allowing their specific isolation and expansion¹⁰. We show here that IFN-γ⁺ but not IFN-γ⁻ 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-γ capture assay.