Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice

Cancer Immun. 2002 Feb 22;2:1.

Abstract

Treatment with monoclonal antibodies (mAbs) specific for CD25 (anti-CD25 mAb) has been shown to suppress growth of a variety of different tumours in mice. These studies did not however determine whether or not anti-CD25 mAbs facilitate tumour rejection by depletion of regulatory T cells or by binding to tumour-specific effector cells. Using a murine model of melanoma we have found that treatment of mice with anti-CD25 mAb facilitates long-term CD4+ T cell-mediated tumour immunity through depletion of CD25+ regulatory cells. We further show that the effector CD4+ T cells confer long-term tumour immunity even in the presence of CD25+ regulatory cells and do not require CD8+ T cells for tumour rejection. The inhibitory impact of anti-CD25 mAb treatment on tumour growth may be the result of depleting CD25+ regulatory cells that normally inhibit the generation of immune responses to self-antigens that are shared by the tumour. We have performed experiments to determine whether or not immune responses to melanocyte antigens are generated in anti-CD25 mAb-treated, melanoma-immune mice. The results of the experiments indicate that a T cell response to the melanocyte antigen tyrosinase accompanies suppression of tumour growth in mice lacking CD25+ regulatory cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, Differentiation
  • CD4-Positive T-Lymphocytes / immunology*
  • Disease Models, Animal
  • Female
  • Genetic Vectors
  • Immunotherapy
  • Melanoma / immunology
  • Melanoma / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Monophenol Monooxygenase / therapeutic use
  • Neoplasm Transplantation
  • Neoplasms, Second Primary / prevention & control
  • Receptors, Interleukin-2 / immunology*
  • Recombinant Proteins / therapeutic use
  • T-Lymphocytes / immunology
  • Tumor Cells, Cultured
  • Vaccinia virus / genetics

Substances

  • Antibodies, Monoclonal
  • Antigens, Differentiation
  • Receptors, Interleukin-2
  • Recombinant Proteins
  • Monophenol Monooxygenase