title: Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients.
abstract: 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.
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. le.odunsi@roswellpark.org
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.forename: Junko
authors.initials: J
authors.lastname: Matsuzaki
authors.forename: Julia
authors.initials: J
authors.lastname: Karbach
authors.forename: Antje
authors.initials: A
authors.lastname: Neumann
authors.forename: Paulette
authors.initials: P
authors.lastname: Mhawech-Fauceglia
authors.forename: Austin
authors.initials: A
authors.lastname: Miller
authors.forename: Amy
authors.initials: A
authors.lastname: Beck
authors.forename: Carl D
authors.initials: CD
authors.lastname: Morrison
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Heidi
authors.initials: H
authors.lastname: Godoy
authors.forename: Shashikant
authors.initials: S
authors.lastname: Lele
authors.forename: Nefertiti
authors.initials: N
authors.lastname: duPont
authors.forename: Robert
authors.initials: R
authors.lastname: Edwards
authors.forename: Protul
authors.initials: P
authors.lastname: Shrikant
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Elke
authors.initials: E
authors.lastname: Jäger
mesh_terms: D000917:Antibody Formation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005587:Fowlpox virus / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D008565:Membrane Proteins / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D016896:Treatment Outcome; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D018984:Epitopes, T-Lymphocyte; D008565:Membrane Proteins; D014614:Vaccines, Synthetic