CD4+ T cell-mediated HER-2/neu-specific tumor rejection in the absence of B cells

Int J Cancer. 2004 Mar 20;109(2):259-64. doi: 10.1002/ijc.11654.

Abstract

HER-2/neu (HER-2) is a cell surface proto-oncogene that is often overexpressed in carcinomas. Passive administration of anti-HER-2 antibodies in breast cancer patients has achieved promising results, but less is known about the role of antibodies in active immunization. We asked whether B cells/antibodies are needed for tumor immunity induced by plasmid (HER-2 and GM-CSF) immunization. HER-2 specific tumor immunity relied completely on both CD4+ and CD8+ T cells. IFN-gamma, and to a lesser extent IL-4, seemed to be crucial cytokines during tumor rejection. Protection was associated with production of anti-HER-2 IgG antibodies in B cell competent mice. After immunization, however, B cell-deficient mice rejected HER-2-expressing tumors as efficiently as control littermates. We conclude that T cells are the main effector cells in DNA vaccine induced immunity against HER-2 and that anti HER-2 antibodies are not necessary to elicit a protective anti tumor immune response in this model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • B-Lymphocytes / physiology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Humans
  • Immunity, Cellular
  • Interferon-gamma / metabolism
  • Lymphocyte Depletion
  • Male
  • Mammary Neoplasms, Experimental / immunology
  • Mammary Neoplasms, Experimental / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Plasmids
  • Proto-Oncogene Mas
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / immunology
  • Survival Rate
  • Vaccination*
  • Vaccines, DNA / administration & dosage*

Substances

  • Antibodies, Monoclonal
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Vaccines, DNA
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Receptor, ErbB-2