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

Kunle Odunsi, Junko Matsuzaki, Julia Karbach, Antje Neumann, Paulette Mhawech-Fauceglia, Austin Miller, Amy Beck, Carl D. Morrison, Gerd Ritter, Heidi Godoy, Shashikant Lele, Nefertiti DuPont, Robert Edwards, Protul Shrikant, Lloyd J. Old, Sacha Gnjatic, Elke Jäger

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

Recombinant poxviruses (vaccinia and fowlpox) expressing tumorassociated 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.

Original languageEnglish (US)
Pages (from-to)5797-5802
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number15
DOIs
StatePublished - Apr 10 2012

Keywords

  • Effector function
  • T cell epitopes

ASJC Scopus subject areas

  • General

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    Odunsi, K., Matsuzaki, J., Karbach, J., Neumann, A., Mhawech-Fauceglia, P., Miller, A., Beck, A., Morrison, C. D., Ritter, G., Godoy, H., Lele, S., DuPont, N., Edwards, R., Shrikant, P., Old, L. J., Gnjatic, S., & Jäger, E. (2012). Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients. Proceedings of the National Academy of Sciences of the United States of America, 109(15), 5797-5802. https://doi.org/10.1073/pnas.1117208109