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

Nat Med. 2001 Oct;7(10):1159-62. doi: 10.1038/nm1001-1159.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / therapy
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / therapy
  • Female
  • Fibrosarcoma / immunology
  • Fibrosarcoma / therapy
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Interferon-gamma / immunology*
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / therapy
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured

Substances

  • Interferon-gamma