Overlapping synthetic peptides encoding TPD52 as breast cancer vaccine in mice: Prolonged survival |
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Authors: | Saied Mirshahidi Victor G Kramer James B Whitney Sosthène Essono Sandra Lee Glenn Dranoff Karen S Anderson Ruth M Ruprecht |
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Institution: | 1. Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, United States;2. Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115, United States;3. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, United States;4. Harvard School of Public Health, 44 Binney Street, Boston, MA 02115, United States;5. Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, United States |
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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. |
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