Immunological consolidation of ovarian carcinoma recurrences with monoclonal anti-idiotype antibody ACA125: Immune responses and survival in palliative treatment

The aim of the present study was to assess whether the induction of specifi c 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 carci noma. Forty-two patients with platinum-pretreated recurrences were included in a clinical Phase I/II trial of consolidation in third-line therapy. Pat ients initially received four immunizations with 2 mg of alum-precipitated anti-idiotype ACA125 every 2 weeks and then monthly applications. No seriou s allergic reactions could be detected within a maximal control period of 5 6 months. Hyperimmune sera of 27 of 42 patients (61.2%) showed increased co ncentrations of human antimouse antibodies. Specific anti-anti-idiotypic an tibodies as a marker for induced immunity were detected in 28 of 42 patient s (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 su rvival 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 a nti-CA125 immunity (P < 0.0001), According to these results, vaccination wi th a suitable anti-idiotypic antibody offers an effective way to induce spe cific immunity against a primarily nonimmunogenic tumor antigen such as CA1 25 and is associated with a positive impact on the survival of patients wit h recurrent ovarian cancer with few side effects, which warrants a Phase II I trial for ovarian cancer patients after primary therapy.