Cancer Immunology, Immunotherapy

, Volume 53, Issue 6, pp 490–496

Ii-Key/HER-2/neu MHC class-II antigenic epitope vaccine peptide for breast cancer

  • Michael E. Gillogly
  • Nikoletta L. Kallinteris
  • Minzhen Xu
  • Joseph V. Gulfo
  • Robert E. Humphreys
  • James L. Murray
Original Article

DOI: 10.1007/s00262-003-0463-y

Cite this article as:
Gillogly, M.E., Kallinteris, N.L., Xu, M. et al. Cancer Immunol Immunother (2004) 53: 490. doi:10.1007/s00262-003-0463-y

Abstract

Purpose

Cytotoxic T lymphocytes (CTL)- and T-helper cell-specific, and major histocompatibility complex (MHC) class-I and class-II peptides, respectively, of the HER-2/neu protein, induce immune responses in patients. A major challenge in developing cancer peptide vaccines is breaking tolerance to tumor-associated antigens which are functionally self-proteins. An adequate CD4+ T-helper response is required for effective and lasting responses.

Methods

Stimulating anti-cancer CD4+ T cell responses by MHC class-II epitope peptides has been limited by their weak potency, at least compared with tight-binding MHC class-I epitope peptides. Previously, a potent T-cell response to a MHC class-II epitope was engineered by coupling the N-terminus of the pigeon cytochrome C [PGCC(95–104)] MHC class-II epitope to the C-terminus of an immunoregulatory segment of the Ii protein (hIi77–81, the Ii-Key peptide) through a polymethylene spacer.

Results

In vitro presentation of the MHC class-II epitope to a T hybridoma was enhanced greatly (>250 times). Now, an Ii-Key/HER-2/neu (777–789) MHC class-II epitope hybrid peptide stimulated lymphocytes from both a healthy donor and a patient with metastatic breast carcinoma. The in vitro primary stimulation with the hybrid peptide strongly activated IFN-γ release, whereas the epitope-only peptide was weakly active. In fact, the hybrid stimulated IFN-γ release as well as the wild-type peptide when augmented with IL-12; however, the hybrid was comparable to free peptide in stimulating IL-4 release. This pattern is consistent with preferential activation along a non-tolerogenic Th1 pathway.

Conclusion

Such Ii-Key/MHC class-II epitope hybrid peptides have both diagnostic and therapeutic applications.

Keywords

HER-2/neu Breast cancer Cancer vaccine MHC class II Antigenic peptide 

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Michael E. Gillogly
    • 1
  • Nikoletta L. Kallinteris
    • 2
  • Minzhen Xu
    • 2
  • Joseph V. Gulfo
    • 2
  • Robert E. Humphreys
    • 2
  • James L. Murray
    • 1
  1. 1.M.D. Anderson Cancer CenterHoustonUSA
  2. 2.Antigen Express Inc.WorcesterUSA