Expansion of HER2/neu-specific T cells ex vivo following immunization with a HER2/neu peptide-based vaccine

Clin Breast Cancer. 2001 Apr;2(1):73-9. doi: 10.3816/CBC.2001.n.014.


The identification and characterization of tumor antigens has facilitated the development of immune-based cancer prophylaxis and therapy. Cancer vaccines, like viral vaccines, may be effective in cancer prevention. Adoptive T-cell therapy, in contrast, may be more efficacious for the eradication of existing malignancies. Our group is examining the feasibility of antigen-specific adoptive T-cell therapy for the treatment of established cancer in the HER2/neu model. Transgenic mice overexpressing rat neu in mammary tissue develop malignancy, histologically similar to human HER2/neu-overexpressing breast cancer. These mice can be effectively immunized against a challenge with neu-positive tumor cells. Adoptive transfer of neu-specific T cells into tumor-bearing mice eradicates malignancy. Effective T-cell therapy relies on optimization of the ex vivo expansion of antigen-specific T cells. Two important elements of ex vivo antigen-specific T-cell growth that have been identified are (1) the preexisting levels of antigen-specific T cells and (2) the cytokine milieu used during ex vivo expansion of the T cells. Phase I clinical trials of HER2/neu-based peptide vaccination in human cancer patients have demonstrated that increased levels of HER2/neu-specific T-cells can be elicited after active immunization. Initiating cultures with greater numbers of antigen-specific T cells facilitates expansion. In addition, cytokines, such as interleukin-12, when added during ex vivo culturing along with interleukin-2 can selectively expand antigen-specific T-cells. Interleukin-12 also enhances antigen-specific functional measurements such as interferon-gamma and tumor necrosis factor-alpha release. Refinements in ex vivo expansion techniques may greatly improve the feasibility of tumor-antigen T-cell-based therapy for the treatment of advanced-stage HER2/neu-overexpressing breast malignancy.

Publication types

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

MeSH terms

  • Animals
  • Cancer Vaccines / therapeutic use*
  • Clinical Trials as Topic
  • Cytokines / metabolism
  • Humans
  • Immunization
  • Immunotherapy, Adoptive / methods
  • Mice
  • Mice, Transgenic
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Peptide Fragments / pharmacology
  • Peptides / immunology
  • Receptor, ErbB-2 / immunology*
  • T-Lymphocytes / immunology*


  • Cancer Vaccines
  • Cytokines
  • Peptide Fragments
  • Peptides
  • Receptor, ErbB-2