Combinations of tumor-specific CD8+ CTLs and anti-CD25 mAb provide improved immunotherapy

Oncol Rep. 2008 May;19(5):1265-70.

Abstract

One new approach to cancer therapy is based on the adoptive transfer of tumor-specific cytotoxic T cells and anti-CD25 antibodies. In the present study, CD8+ and IFN-gamma secreting T lymphocytes (CTLs) were enriched as tumor-specific cytotoxic T cells from spleen lymphocytes of mice bearing the Renca tumor (a murine renal carcinoma line originating from a BALB/c mouse) after stimulation with tumor cells. An anti-CD25 IL-2Ralpha(anti-CD25) mAb from hybridoma PC61 was used for depletion for CD4(+)CD25(+) regulatory T (Treg) cells. Treatment-efficacy for tumor-bearing mice was compared using 4 systems: 1, whole spleen lymphocytes stimulated with tumor cells in vitro from tumor-bearing mice; 2, CTLs; 3, anti-CD25 mAbs; 4, CTLs and anti-CD25 mAbs. At the 50th day after tumor inoculation, in the group which received anti-CD25 mAb for depletion of T cells and inoculation of CTLs, tumors had disappeared and no re-growth was observed. In contrast, all mice of the non-treated and other three groups, treated with whole spleen cells alone, CTLs alone and anti-CD25 mAb alone, had died. These results showed that a combination of Treg cell-depletion using anti-CD25 mAbs and CTL administration is a feasible approach for treatment of cancers which warrants further exploration in the clinical setting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology*
  • Cell Line, Tumor
  • Chromium Isotopes / chemistry
  • Female
  • Immunotherapy, Adoptive / methods
  • Interferon-gamma / metabolism
  • Interleukin-2 Receptor alpha Subunit / biosynthesis*
  • Medical Oncology / methods
  • Mice
  • Mice, Inbred BALB C
  • Models, Biological
  • T-Lymphocytes, Cytotoxic / metabolism*
  • T-Lymphocytes, Regulatory / cytology*

Substances

  • Antibodies, Monoclonal
  • Chromium Isotopes
  • Interleukin-2 Receptor alpha Subunit
  • Interferon-gamma