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Immunological Consolidation of Ovarian Carcinoma Recurrences with Monoclonal Anti-Idiotype Antibody ACA125: Immune Responses and Survival in Palliative Treatment¹

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.

Department of Obstetrics and Gynecology, University of Tuebingen, 72076 Tuebingen, Germany [U. W., S. K., S. R., P. G., J. H., K. R., H. S., D. W.]; Department of Obstetrics and Gynecology [T. B., D. K.] and Clinic of Nuclear Medicine [H-J. B.], University of Bonn, 53105 Bonn, Germany; and Department of Obstetrics and Gynecology, University of Ulm, 89075 Ulm, Germany [V. M., R. K.]

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.

Commentary

Are Solid Tumor Anti-Idiotype Vaccines Ready for Prime Time?: Commentary re: U. Wagner et al., Immunological Consolidation of Ovarian Carcinoma Recurrences with Monoclonal Anti-Idiotype Antibody ACA125: Immune Responses and Survival in Palliative Treatment. Clin. Cancer Res., 7: 1154–1162, 2001.

Kenneth A. Foon and Malaya Bhattacharya-Chatterjee
Clin. Cancer Res. 2001 7: 1112-1115. [Full Text] [PDF]

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