title: Tumor-cell number and viability as quality and efficacy parameters of autologous virus-modified cancer vaccines in patients with breast or ovarian cancer.
abstract: OBJECTIVE
  We investigated quality and efficacy criteria of an autologous, physically and immunologically purified, Newcastle disease virus (NDV)-modified, irradiated tumor-cell vaccine (ATV-NDV) by analyzing three independent cohorts (a through c) of patients vaccinated between 1991 and 1995.
  
  
  METHODS
  Included were 63 patients with primary breast cancer (a), 27 with metastatic pretreated breast cancer (b), and 31 with metastatic pretreated ovarian cancer (c). In addition to vaccine, cohorts b and c received nonspecific immunotherapy as supportive treatment. After cryoconservation and purification, the vaccines varied in applied numbers of viable cells and dead cell contaminations. We retrospectively hypothesized that an immunogenic vaccine should contain at least 1.5 x 10(6) viable tumor cells and viability should be at least 33%. Each cohort was thus divided into two groups; one that received vaccine type A (A), fulfilling both criteria; and the other type B (B), missing one or both criteria.
  
  
  RESULTS
  Conventional prognostic factors were wall balanced between A and B in cohorts a and c. In cohort a, there was a benefit in survival (P = .026) and disease-free survival (P = .089) for A. In addition, in cohort a, the relative risk of dying in the group that received A as compared with B was 0.2 (univariate Cox model). There were also survival trends in favor of A versus B (P = .18 and P = .09, respectively) in cohorts b and c, with relative risks of 0.5 and 0.42, respectively. In cohort b, the survival benefit could not be ascribed to vaccine quality alone, because of prognostic imbalance in favor of A.
  
  
  CONCLUSIONS
  In cohort c, like in cohort a, the survival benefit for A may be ascribed to the ATV-NDV vaccine quality, since prognostic factors were not biased. This could imply clinical effectivity in breast and ovarian cancer with ATV-NDV high-quality vaccine. Furthermore, the data provide clinically relevant information for standardization and quality control of autologous tumor-cell vaccines. A randomized study is urgently needed.
authors.affiliation: Universitäts-Frauenklinik Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Ahlert
authors.forename: W
authors.initials: W
authors.lastname: Sauerbrei
authors.forename: G
authors.initials: G
authors.lastname: Bastert
authors.forename: S
authors.initials: S
authors.lastname: Ruhland
authors.forename: B
authors.initials: B
authors.lastname: Bartik
authors.forename: N
authors.initials: N
authors.lastname: Simiantonaki
authors.forename: J
authors.initials: J
authors.lastname: Schumacher
authors.forename: B
authors.initials: B
authors.lastname: Häcker
authors.forename: M
authors.initials: M
authors.lastname: Schumacher
authors.forename: V
authors.initials: V
authors.lastname: Schirrmacher
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019496:Cancer Vaccines / Q000592:standards* / Q000627:therapeutic use; D015331:Cohort Studies; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D009522:Newcastle disease virus / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines