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

AbstractPURPOSE:
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-gamma release, whereas the epitope-only peptide was weakly active. In fact, the hybrid stimulated IFN-gamma 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.
AuthorsMichael E Gillogly, Nikoletta L Kallinteris, Minzhen Xu, Joseph V Gulfo, Robert E Humphreys, James L Murray
JournalCancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 53 Issue 6 Pg. 490-6 (Jun 2004) ISSN: 0340-7004 [Print] Germany
PMID14740174 (Publication Type: Journal Article)
Chemical References
  • Antigens, Differentiation, B-Lymphocyte
  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes
  • Histocompatibility Antigens Class II
  • Recombinant Fusion Proteins
  • Vaccines, Subunit
  • invariant chain
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma
  • Receptor, ErbB-2
Topics
  • Antigens, Differentiation, B-Lymphocyte (immunology)
  • Antigens, Neoplasm (immunology)
  • Breast Neoplasms (immunology, pathology, secondary)
  • Cancer Vaccines (immunology)
  • Cell Division (immunology)
  • Epitopes (immunology)
  • Female
  • Histocompatibility Antigens Class II (immunology)
  • Humans
  • Immunization
  • Interferon-gamma (metabolism)
  • Interleukin-12 (pharmacology)
  • Interleukin-4 (metabolism)
  • Lymph Nodes (immunology, metabolism, pathology)
  • Lymphocyte Activation (drug effects)
  • Male
  • Receptor, ErbB-2 (immunology)
  • Recombinant Fusion Proteins (immunology)
  • Vaccines, Subunit (immunology)

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