title: Overlapping synthetic peptides encoding TPD52 as breast cancer vaccine in mice: prolonged survival.
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)-gamma 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.
authors.affiliation: Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, United States.
authors.forename: Saied
authors.initials: S
authors.lastname: Mirshahidi
authors.forename: Victor G
authors.initials: VG
authors.lastname: Kramer
authors.forename: James B
authors.initials: JB
authors.lastname: Whitney
authors.forename: Sosthène
authors.initials: S
authors.lastname: Essono
authors.forename: Sandra
authors.initials: S
authors.lastname: Lee
authors.forename: Glenn
authors.initials: G
authors.lastname: Dranoff
authors.forename: Karen S
authors.initials: KS
authors.lastname: Anderson
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Ruprecht
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000096:biosynthesis / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000939:Epitopes / Q000276:immunology; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D052119:Lysosomal-Associated Membrane Protein 2 / Q000276:immunology; D051907:Lysosomal Membrane Proteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics; D013534:Survival; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000235:genetics*; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D016827:CD8 Antigens; D019496:Cancer Vaccines; D000939:Epitopes; D007371:Interferon-gamma; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C114751:TPD52 protein, human