Immunological consolidation of ovarian carcinoma recurrences with monoclonal anti-idiotype antibody ACA125: immune responses and survival in palliative treatment. See The biology behind: K. A. Foon and M. Bhattacharya-Chatterjee, Are solid tumor anti-idiotype vaccines ready for prime time? Clin. Cancer Res., 7:1112-1115, 2001.
The aim of the present study was to assess whether the induction of specific immune responses by vaccination with the murine monoclonal anti-idiotypic antibody ACA125, which imitates the tumor-associated antigen CA125, has a positive influence on the survival of patients with recurrent ovarian carcinoma. Forty-two patients with platinum-pretreated recurrences were included in a clinical Phase I/II trial of consolidation in third-line therapy. Patients initially received four immunizations with 2 mg of alum-precipitated anti-idiotype ACA125 every 2 weeks and then monthly applications. No serious allergic reactions could be detected within a maximal control period of 56 months. Hyperimmune sera of 27 of 42 patients (64.2%) showed increased concentrations of human antimouse antibodies. Specific anti-anti-idiotypic antibodies as a marker for induced immunity were detected in 28 of 42 patients (66.7%). The survival of the whole ACA125-treated collective of patients after a mean of 12.6 antibody applications was 14.9 +/- 12.9 months. The survival of patients with a positive immune response was 19.9 +/- 13.1 months in contrast with 5.3 +/- 4.3 months in those patients without detectable anti-CA125 immunity (P < 0.0001). According to these results, vaccination with a suitable anti-idiotypic antibody offers an effective way to induce specific immunity against a primarily nonimmunogenic tumor antigen such as CA125 and is associated with a positive impact on the survival of patients with recurrent ovarian cancer with few side effects, which warrants a Phase III trial for ovarian cancer patients after primary therapy.
Wagner
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Department of Obstetrics and Gynecology, University of Tuebingen, 72076 Tuebingen, Germany. sekr.oawagner@med.uni-tuebingen.de
Köhler
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Reinartz
S
S
Giffels
P
P
Huober
J
J
Renke
K
K
Schlebusch
H
H
Biersack
H J
HJ
Möbus
V
V
Kreienberg
R
R
Bauknecht
T
T
Krebs
D
D
Wallwiener
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D
D000888:Antibodies, Anti-Idiotypic / Q000009:adverse effects / Q000627:therapeutic use*; D018394:CA-125 Antigen / Q000276:immunology; D005260:Female; D006801:Humans; D007109:Immunity; D007167:Immunotherapy; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D010166:Palliative Care; D012008:Recurrence; D015996:Survival Rate; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D018394:CA-125 Antigen