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: Mohan Karkada, Genevieve M Weir, Tara Quinton, Leeladhar Sammatur, Lisa D MacDonald, Alecia Grant, Robert Liwski, Ridas Juskevicius, Gomathinayagam Sinnathamby, Ramila Philip, Marc Mansour
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 33 Issue 3 Pg. 250-61 (Apr 2010) ISSN: 1537-4513 [Electronic] United States
• PMID: 20445345 (Publication Type: Journal Article)

Chemical References

• Cancer Vaccines
• DPX-0907
• HLA-A Antigens
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• Oligopeptides
• Vaccines, Subunit
• Interferon-gamma

Topics

• Amino Acid Sequence
• Animals
• Breast Neoplasms (immunology, pathology, prevention & control)
• CD8-Positive T-Lymphocytes (drug effects, immunology, metabolism)
• Cancer Vaccines (administration & dosage, immunology)
• Cell Line, Tumor
• Enzyme-Linked Immunosorbent Assay
• Female
• HLA-A Antigens (genetics, immunology)
• HLA-A2 Antigen
• Humans
• Interferon-gamma (metabolism)
• Leukocytes, Mononuclear (cytology, drug effects, immunology)
• Mice
• Mice, Transgenic
• Molecular Sequence Data
• Oligopeptides (administration & dosage, chemical synthesis, immunology)
• Ovarian Neoplasms (immunology, pathology, prevention & control)
• Rats
• T-Lymphocytes, Cytotoxic (cytology, drug effects, immunology)
• T-Lymphocytes, Regulatory (drug effects, immunology, metabolism)
• Vaccination (methods)
• Vaccines, Subunit (administration & dosage, immunology)