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[sup.+] 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[sup.+] 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][sup.+] but not IFN-[gamma][sup.-] 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.
Author(s): Christian Becker [1]; Heike Pohla [2]; Bernhard Frankenberger [3]; Thomas Schuler [1]; Mario Assenmacher [4]; Dolores J. Schendel [3]; Thomas Blankenstein (corresponding author) [1, 5] In the CT26 tumor [...]