title: Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMax encapsulated CTL/T helper peptides.
abstract: The incidence of cancer increases significantly in later life, yet few pre-clinical studies of cancer immunotherapy use mice of advanced age. A novel vaccine delivery platform (VacciMax,VM) is described that encapsulates antigens and adjuvants in multilamellar liposomes in a water-in-oil emulsion. The therapeutic potential of VM-based vaccines administered as a single dose was tested in HLA-A2 transgenic mice of advanced age (48-58 weeks old) bearing large palpable TC1/A2 tumors. The VM-based vaccines contained one or more peptides having human CTL epitopes derived from HPV 16 E6 and E7. VM formulations contained a single peptide, a mixture of four peptides or the same four peptides linked together in a single long peptide. All VM formulations contained PADRE and CpG as adjuvants and ISA51 as the hydrophobic component of the water-in-oil emulsion. VM-formulated vaccines containing the four peptides as a mixture or linked together in one long peptide eradicated 19-day old established tumors within 21 days of immunization. Peptide-specific cytotoxic cellular responses were confirmed by ELISPOT and intracellular staining for IFN-gamma producing CD8+ T cells. Mice rendered tumor-free by vaccination were re-challenged in the opposite flank with 10 million HLF-16 tumor cells, another HLA-A2/E6/E7 expressing tumor cell line. None of these mice developed tumors following the re-challenge. In summary, this report describes a VM-formulated therapeutic vaccine with the following unprecedented outcome: a) eradication of large tumors (> 700 mm3) b) in mice of advanced age c) in less than three weeks post-immunization d) following a single vaccination.
authors.affiliation: ImmunoVaccine Technologies Inc., Halifax, NS, B3J 3R1, Canada. Pd.ivt@immunovaccine.com
authors.forename: Pirouz M
authors.initials: PM
authors.lastname: Daftarian
authors.forename: Marc
authors.initials: M
authors.lastname: Mansour
authors.forename: Bill
authors.initials: B
authors.lastname: Pohajdak
authors.forename: Antar
authors.initials: A
authors.lastname: Fuentes-Ortega
authors.forename: Ella
authors.initials: E
authors.lastname: Korets-Smith
authors.forename: Lisa
authors.initials: L
authors.lastname: Macdonald
authors.forename: Genevieve
authors.initials: G
authors.lastname: Weir
authors.forename: Robert G
authors.initials: RG
authors.lastname: Brown
authors.forename: W Martin
authors.initials: WM
authors.lastname: Kast
mesh_terms: D000375:Aging / Q000276:immunology / Q000473:pathology; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000295:instrumentation*; D007371:Interferon-gamma / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology*; D010455:Peptides / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013194:Staining and Labeling; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D010455:Peptides; D007371:Interferon-gamma