title: Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (phase Ib/II).
abstract: OBJECTIVE
  A Phase I/IIb multicenter study was conducted to evaluate the safety and immunogenicity of the anti-idiotypic antibody vaccine ACA125 that functionally imitates the tumor antigen CA125 in 119 patients with advanced ovarian carcinoma. A preliminary report on the initial 42 patients demonstrated safety and immunogenicity.
  
  
  METHODS
  Using the complete intention-to-treat population (n = 119) who received a mean of 9.7 ACA125 applications, survival was analyzed with respect to immunological responses.
  
  
  RESULTS
  In 81 patients (68.1%), a specific anti-anti-idiotypic antibody (Ab3) response could be induced. Additionally, the development of CA125-specific antibodies (Ab1') and antibody-dependent cell-mediated cytotoxicity of CA125-positive tumor cells was observed in 50.4% and 26.9% of patients, respectively. The median survival of all patients was 19.4 months (range, 0.5-56.1 months). Ab3-positive patients showed a significantly longer survival (median, 23.4 months; P < 0.0001) as compared with Ab3-negative patients (median, 4.9 months). A positive Ab3 response remained associated with longer survival when controlling for other prognostic factors including FIGO (International Federation of Gynecologists and Obstetricians) stage, response to and type of first-line chemotherapy, number of previous treatments, or concomitant antitumor therapy. With regard to safety, repeated vaccination was well tolerated. No serious adverse events related to the application of ACA125 occurred.
  
  
  CONCLUSIONS
  Although the uncontrolled design of this study prevents definitive conclusions with respect to subgroups, the data support a relationship between Ab3 response and survival time. Thus, the need for further randomized, controlled clinical trials to establish efficacy of the vaccine ACA125 seems to be indicated.
authors.affiliation: Center of Obstetrics and Gynecology, University of Marburg, Marburg, Germany. reinartz@med.uni-marburg.de
authors.forename: Silke
authors.initials: S
authors.lastname: Reinartz
authors.forename: Siegmund
authors.initials: S
authors.lastname: Köhler
authors.forename: Harald
authors.initials: H
authors.lastname: Schlebusch
authors.forename: Karl
authors.initials: K
authors.lastname: Krista
authors.forename: Patrick
authors.initials: P
authors.lastname: Giffels
authors.forename: Kirsten
authors.initials: K
authors.lastname: Renke
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Volker
authors.initials: V
authors.lastname: Möbus
authors.forename: Rolf
authors.initials: R
authors.lastname: Kreienberg
authors.forename: Andreas
authors.initials: A
authors.lastname: DuBois
authors.forename: Paul
authors.initials: P
authors.lastname: Sabbatini
authors.forename: Uwe
authors.initials: U
authors.lastname: Wagner
mesh_terms: D000818:Animals; D018394:CA-125 Antigen / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use / Q000633:toxicity*; D005260:Female; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
chemical_list: D018394:CA-125 Antigen; D019496:Cancer Vaccines; D007518:Isoantibodies