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Induction of effective and antigen-specific antitumour immunity by a liposomal ErbB2/HER2 peptide-based vaccination construct.

Abstract
Efficient delivery of tumour-associated antigens to appropriate cellular compartments of antigen-presenting cells is of prime importance for the induction of potent, cell-mediated antitumour immune responses. We have designed novel multivalent liposomal constructs that co-deliver the p63-71 cytotoxic T Lymphocyte epitope derived from human ErbB2 (HER2), and HA307-319, a T-helper (Th) epitope derived from influenza haemagglutinin. Both peptides were conjugated to the surface of liposomes via a Pam3CSS anchor, a synthetic lipopeptide with potent adjuvant activity. In a murine model system, vaccination with these constructs completely protected BALB/c mice from subsequent s.c. challenge with ErbB2-expressing, but not ErbB2-negative, murine renal carcinoma (Renca) cells, indicating the induction of potent, antigen-specific immune responses. I.v. re-challenge of tumour-free animals 2 months after the first tumour cell inoculation did not result in the formation of lung tumour nodules, suggesting that long-lasting, systemic immunity had been induced. While still protecting the majority of vaccinated mice, a liposomal construct lacking the Th epitope was less effective than the diepitope construct, also correlating with a lower number of CD8+ IFN-gamma+ T-cells identified upon ex vivo peptide restimulation of splenocytes from vaccinated animals. Importantly, in a therapeutic setting treatment with the liposomal vaccines resulted in cures in the majority of tumour-bearing mice and delayed tumour growth in the remaining ones. Our results demonstrate that liposomal constructs which combine Tc and Th peptide antigens and lipopeptide adjuvants can induce efficient, antigen-specific antitumour immunity, and represent promising synthetic delivery systems for the design of specific antitumour vaccines.
AuthorsA Roth, F Rohrbach, R Weth, B Frisch, F Schuber, W S Wels
JournalBritish journal of cancer (Br J Cancer) Vol. 92 Issue 8 Pg. 1421-9 (Apr 25 2005) ISSN: 0007-0920 [Print] England
PMID15812545 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins, Viral
  • Liposomes
  • Peptide Fragments
  • Peptides
  • influenza hemagglutinin (307-319)
  • Receptor, ErbB-2
Topics
  • Animals
  • Cancer Vaccines (therapeutic use)
  • Carcinoma, Renal Cell (drug therapy, immunology)
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte (immunology)
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins, Viral (immunology)
  • Humans
  • Kidney Neoplasms (drug therapy, immunology)
  • Liposomes (immunology)
  • Mice
  • Mice, Inbred BALB C
  • Peptide Fragments (immunology)
  • Peptides (immunology)
  • Receptor, ErbB-2 (immunology)
  • T-Lymphocytes, Cytotoxic (immunology)
  • T-Lymphocytes, Helper-Inducer (immunology)

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