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

116 Citations (Scopus)

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
Externally publishedYes

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Fowlpox
Vaccinia
Ovarian Neoplasms
Melanoma
Vaccination
Antigens
Viral Vaccines
Poxviridae
T-Lymphocytes
Phase II Clinical Trials
Cancer Vaccines
Neoplasms
Clinical Trials

Keywords

  • Effector function
  • T cell epitopes

ASJC Scopus subject areas

  • General

Cite this

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

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 15, 10.04.2012, p. 5797-5802.

Research output: Contribution to journalArticle

Odunsi, K, Matsuzaki, J, Karbach, J, Neumann, A, Mhawech-Fauceglia, P, Miller, A, Beck, A, Morrison, CD, Ritter, G, Godoy, H, Lele, S, DuPont, N, Edwards, R, Shrikant, P, Old, LJ, 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, vol. 109, no. 15, pp. 5797-5802. https://doi.org/10.1073/pnas.1117208109
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. / Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 15. pp. 5797-5802.
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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.",
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