Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients

Recombinant poxviruses (vaccinia and fowlpox) expressing tumor-associated antigens are currently being evaluated in clinical trials as cancer vaccines to induce tumor-specific immune responses that will improve clinical outcome. To test whether a diversified prime and boost regimen targeting NY-ESO-...

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Published in:	Proceedings of the National Academy of Sciences - PNAS 2012-04, Vol.109 (15), p.5797-5802
Main Authors:	Odunsi, Kunle, Matsuzaki, Junko, Karbach, Julia, Neumann, Antje, Mhawech-Fauceglia, Paulette, Miller, Austin, Beck, Amy, Morrison, Carl D, Ritter, Gerd, Godoy, Heidi, Lele, Shashikant, duPont, Nefertiti, Edwards, Robert, Shrikant, Protul, Old, Lloyd J, Gnjatic, Sacha, Jäger, Elke
Format:	Article
Language:	eng
Subjects:	animal ovaries Antibodies Antibody Formation - immunology Antigen (tumor-associated) Antigens Antigens, Neoplasm - immunology Biological Sciences Cancer Cancer vaccines CD4 antigen CD4-Positive T-Lymphocytes - immunology CD8 antigen CD8-positive T-lymphocytes CD8-Positive T-Lymphocytes - immunology Clinical trials Data processing Disease remission Epitopes Epitopes, T-Lymphocyte - immunology Female fowl pox Fowlpox Fowlpox virus - genetics Genetic Vectors - genetics Humans Immune response Lymphocytes T Melanoma Melanoma - immunology Melanoma - pathology Membrane Proteins - immunology NY-ESO-1 protein Ovarian cancer Ovarian diseases ovarian neoplasms Ovarian Neoplasms - immunology Ovarian Neoplasms - pathology patients Poxviridae risk Risk factors secondary immunization Skin cancer T cell receptors T lymphocytes Treatment Outcome Tumors Vaccination Vaccines Vaccines, Synthetic - immunology Vaccinia Vaccinia virus - genetics
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Summary:	Recombinant poxviruses (vaccinia and fowlpox) expressing tumor-associated antigens are currently being evaluated in clinical trials as cancer vaccines to induce tumor-specific immune responses that will improve clinical outcome. To test whether a diversified prime and boost regimen targeting NY-ESO-1 will result in clinical benefit, we conducted two parallel phase II clinical trials of recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1), followed by booster vaccinations with recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) in 25 melanoma and 22 epithelial ovarian cancer (EOC) patients with advanced disease who were at high risk for recurrence/progression. Integrated NY-ESO-1-specific antibody and CD4+ and CD8+ T cells were induced in a high proportion of melanoma and EOC patients. In melanoma patients, objective response rate [complete and partial response (CR+PR)] was 14%, mixed response was 5%, and disease stabilization was 52%, amounting to a clinical benefit rate (CBR) of 72% in melanoma patients. The median PFS in the melanoma patients was 9 mo (range, 0–84 mo) and the median OS was 48 mo (range, 3–106 mo). In EOC patients, the median PFS was 21 mo (95% CI, 16–29 mo), and median OS was 48 mo (CI, not estimable). CD8+ T cells derived from vaccinated patients were shown to lyse NY-ESO-1-expressing tumor targets. These data provide preliminary evidence of clinically meaningful benefit for diversified prime and boost recombinant pox-viral-based vaccines in melanoma and ovarian cancer and support further evaluation of this approach in these patient populations.
ISSN:	0027-8424 1091-6490