Cellular immunity to the Her-2/neu protooncogene

Adv Cancer Res. 2002;85:101-44. doi: 10.1016/s0065-230x(02)85004-7.

Abstract

Her-2/neu (HER-2) is a 185-kDa receptor-like glycoprotein that is overexpressed by a variety of tumors such as breast, ovarian, gastric, and colorectal carcinomas. Overexpression of this oncogene is directly associated with malignant transformation of epithelial cells. The frequency of HER-2 overexpression varies among the different types of cancers, but universally represents a marker of poor prognosis. The critical role of HER-2 in epithelial oncogenesis as well as its selective overexpression on malignant tissues makes it an ideal target for immunotherapy. Antibodies and T cells reactive to HER-2 are known to naturally occur in patients with HER-2 positive tumors, confirming the immunogenicity of the molecule. Both antibodies as well as T cells reactive to HER-2 have been utilized for immunotherapy of HER-2 positive tumors. The "humanized" monoclonal antibody Herceptin has been tested in several clinical trials and found to be an effective adjuvant therapy for HER-2 positive breast and ovarian cancer patients. However, the frequency of patients responding to Herceptin is limited and a majority of patients initially responding to Herceptin develop resistance within a year of treatment. The use of vaccination strategies that generate T cell responses with or without accompanying antibody responses may serve to mitigate the problem. Various strategies for generating T cell-mediated responses against HER-2 are currently being examined in animal models or in clinical trials. The potential advantages of the various approaches to immunotherapy, their pitfalls, and the mechanisms by which HER-2 positive tumors can evade immune responses are discussed in this review.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antigen Presentation
  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / therapeutic use
  • Cell Transformation, Neoplastic
  • Clinical Trials as Topic
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation
  • Genes, erbB-2
  • HLA Antigens / immunology
  • Humans
  • Immunity, Cellular
  • Immunotherapy
  • Ligands
  • Mice
  • Molecular Sequence Data
  • Multigene Family
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Organ Specificity
  • Receptor, ErbB-2 / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Trastuzumab
  • Tumor Escape

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm
  • Cancer Vaccines
  • HLA Antigens
  • Ligands
  • Receptor, ErbB-2
  • Trastuzumab