title: A novel breast/ovarian cancer peptide vaccine platform that promotes specific type-1 but not Treg/Tr1-type responses.
abstract: In light of lack of efficacy associated with current cancer vaccines, we aimed to develop a novel vaccine platform called DepoVax as a therapeutic vaccine for breast/ovarian cancer. This study was designed to examine the efficacy of this novel platform over conventional emulsion vaccine using human class I MHC transgenic mice. We have developed a water-free depot vaccine formulation (DPX-0907) with high immune activating potential. Naturally processed peptides bound to HLA-A2 molecules isolated from independent breast and ovarian tumor cell lines, but not normal cells, were isolated and used as antigens in DPX-0907 along with a proprietary adjuvant and a T helper peptide epitope. Efficacy of vaccine was tested in immunized HLA-A*0201/H2Dd transgenic mice by measuring the frequency of IFN-gamma secreting cells in the draining lymph nodes, and regulatory T-cell frequencies in the spleen. Compared with a water-in-oil emulsion vaccine, DPX-0907 enhanced IFN-gamma+CD8+ T cells in vaccine site-draining lymph nodes, as seen by immunofluorescence staining and increased the frequency of IFN-gamma+ lymph node cells as seen by enzyme-linked immunosorbent spot assay. Notably, while conventional vaccine formulations elicited elevated levels of splenic Foxp3+CD4+ and IL10-secreting T cells, this was not the case for DPX-0907-based vaccines, with treated animals exhibiting normal levels of regulatory T cells. These data support the unique capabilities of a vaccine formulation containing novel tumor peptides and DPX-0907 to elicit type-1 dominated, specific immunity that may represent a potent clinical therapeutic modality for patients with breast or ovarian carcinoma.
authors.affiliation: Inc, Halifax, Canada. mkarkada@imvaccine.com
authors.forename: Mohan
authors.initials: M
authors.lastname: Karkada
authors.forename: Genevieve M
authors.initials: GM
authors.lastname: Weir
authors.forename: Tara
authors.initials: T
authors.lastname: Quinton
authors.forename: Leeladhar
authors.initials: L
authors.lastname: Sammatur
authors.forename: Lisa D
authors.initials: LD
authors.lastname: MacDonald
authors.forename: Alecia
authors.initials: A
authors.lastname: Grant
authors.forename: Robert
authors.initials: R
authors.lastname: Liwski
authors.forename: Ridas
authors.initials: R
authors.lastname: Juskevicius
authors.forename: Gomathinayagam
authors.initials: G
authors.lastname: Sinnathamby
authors.forename: Ramila
authors.initials: R
authors.lastname: Philip
authors.forename: Marc
authors.initials: M
authors.lastname: Mansour
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; C575426:DPX-0907; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D009842:Oligopeptides; D022223:Vaccines, Subunit; D007371:Interferon-gamma