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

• Published in: Vaccine 2009-03, Vol.27 (12), p.1825-1833
• Main Authors: Mirshahidi, Saied, Kramer, Victor G, Whitney, James B, Essono, Sosthène, Lee, Sandra, Dranoff, Glenn, Anderson, Karen S, Ruprecht, Ruth M
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Antibiotics; Antigens; Applied microbiology; Biological and medical sciences; Breast cancer; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Cancer; Cancer Vaccines - genetics; CD4-Positive T-Lymphocytes - immunology; CD8 Antigens - biosynthesis; CD8 Antigens - genetics; CD8-Positive T-Lymphocytes - immunology; Cell growth; Cell Line, Tumor; Cell Proliferation; Epitopes - immunology; Fundamental and applied biological sciences. Psychology; Immune system; Immunization; Immunohistochemistry; Immunotherapy; Interferon-gamma - biosynthesis; Lymphocytes; Lysosomal Membrane Proteins - immunology; Lysosomal-Associated Membrane Protein 2 - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Microbiology; Neoplasm Proteins - genetics; Neoplasm Proteins - immunology; Ovarian cancer; Overlapping synthetic peptides (OSP); Peptides; Proteins; Recombinant Proteins - genetics; Signal transduction; Survival; T-Lymphocytes - immunology; Tumor protein 52; Tumors; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Subunit - genetics
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2009.01.089

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.