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

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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.

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Acknowledgement

The authors gratefully acknowledge the advice of C. Ioannides in performing the analyses and interpreting the results.

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Authors and Affiliations

  1. M.D. Anderson Cancer Center, 1525 Holcombe Blvd., Houston, TX 77030, USA

    Michael E. Gillogly & James L. Murray

  2. Antigen Express Inc., 100 Barber Avenue, Worcester, MA 01606-8783, USA

    Nikoletta L. Kallinteris, Minzhen Xu, Joseph V. Gulfo & Robert E. Humphreys

Authors
  1. Michael E. Gillogly
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  2. Nikoletta L. Kallinteris
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  3. Minzhen Xu
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  4. Joseph V. Gulfo
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  5. Robert E. Humphreys
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  6. James L. Murray
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Corresponding author

Correspondence to Robert E. Humphreys.

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Gillogly, M.E., Kallinteris, N.L., Xu, M. et al. Ii-Key/HER-2/neu MHC class-II antigenic epitope vaccine peptide for breast cancer. Cancer Immunol Immunother 53, 490–496 (2004). https://doi.org/10.1007/s00262-003-0463-y

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  • DOI: https://doi.org/10.1007/s00262-003-0463-y

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