We have generated an
immunoglobulin G1 (
IgG1) murine monoclonal anti-idiotype antibody (Ab2) designated
ACA125, which mimics a specific
epitope on the
tumor-associated
antigen CA125. This
antigen is expressed by most of malignant ovarian
tumors. Patients with CA125-positive
tumors are immunologically tolerant to CA125. We used
ACA125 as a surrogate for the
tumor-associated
antigen CA125 for vaccine therapy of 16 patients with advanced
epithelial ovarian cancer or recurrences. Each of the patients received a minimum of 3
injections up to 19
injections of the complete anti-idiotype MAb
ACA125 at a dosage of 2 mg per injection. Nine of 16 patients developed anti-anti-idiotypic (Ab3) responses to the
ACA125. All 9 patients generated specific anti-CA125 antibody demonstrated by reactivity with purified CA125. Nine of 16 patients developed a CA125-specific cellular immune response by their peripheral blood lymphocytes (PBL) and 3 of 16 showed an increase in
gamma-interferon concentrations accompanied by Ab3 responses. Toxicity was limited to
abdominal pain in one case, which led to the withdrawal of further immunizations. The median progression free survival in those patients, who showed a specific immune response to the
tumor-associated
antigen CA125, was 11.0 +/- 5.6 months without any other
therapy, in contrast to 8.0 +/- 4.2 months in the anti-anti-idiotype negative group. This is the first report of the induction of a specific active immunity to the
tumor-associated
antigen CA125 in patients with advanced
ovarian cancer treated with an anti-idiotype antibody that "mimics" CA125. Patients showed the development of a specific humoral and cellular immune response to an otherwise nonimmunogenic
tumor antigen. The immune responses in patients treated with this anti-idiotype
vaccine, the low rate of side effects, and the improved time to progression after the induction of a specific immune response against the
tumor-associated
antigen CA125 justify follow-up clinical trials in advanced
ovarian cancer patients with
minimal residual disease in an adjuvant approach.