Overlapping synthetic peptides encoding TPD52 as breast cancer vaccine in mice: Prolonged survival

Saied Mirshahidi, Victor G. Kramer, James B. Whitney, Sosthène Essono, Sandra Lee, Glenn Dranoff, Karen S. Anderson, Ruth M. Ruprecht

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Peptide-based vaccines, one of several anti-tumor immunization strategies currently under investigation, can elicit both MHC Class I-restricted (CD8+) and Class II-restricted (CD4+) responses. However, the need to identify specific T-cell epitopes in the context of MHC alleles has hampered the application of this approach. We have tested overlapping synthetic peptides (OSP) representing a tumor antigen as a novel approach that bypasses the need for epitope mapping, since OSP contain all possible epitopes for both CD8+ and CD4+ T cells. Here we report that vaccination of inbred and outbred mice with OSP representing tumor protein D52 (TPD52-OSP), a potential tumor antigen target for immunotherapy against breast, prostate, and ovarian cancer, was safe and induced specific CD8+ and CD4+ T-cell responses, as demonstrated by development of specific cytotoxic T cell (CTL) activity, proliferative responses, interferon (IFN)-γ production and CD107a/b expression in all mice tested. In addition, TPD52-OSP-vaccinated BALB/c mice were challenged with TS/A breast carcinoma cells expressing endogenous TPD52; significant survival benefits were noted in vaccine recipients compared to unvaccinated controls (p < 0.001). Our proof-of-concept data demonstrate the safety and efficacy of peptide library-based cancer vaccines that obviates the need to identify epitopes or MHC backgrounds of the vaccinees. We show that an OSP vaccination approach can assist in the disruption of self-tolerance and conclude that our approach may hold promise for immunoprevention of early-stage cancers in a general population.

Original languageEnglish (US)
Pages (from-to)1825-1833
Number of pages9
JournalVaccine
Volume27
Issue number12
DOIs
StatePublished - Mar 13 2009

Keywords

  • Cancer
  • Overlapping synthetic peptides (OSP)
  • Tumor protein 52
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Overlapping synthetic peptides encoding TPD52 as breast cancer vaccine in mice: Prolonged survival'. Together they form a unique fingerprint.

  • Cite this

    Mirshahidi, S., Kramer, V. G., Whitney, J. B., Essono, S., Lee, S., Dranoff, G., Anderson, K. S., & Ruprecht, R. M. (2009). Overlapping synthetic peptides encoding TPD52 as breast cancer vaccine in mice: Prolonged survival. Vaccine, 27(12), 1825-1833. https://doi.org/10.1016/j.vaccine.2009.01.089