A Monoclonal Antiidiotypic Antibody ACA 125 Mimicking the Tumor-Associated Antigen CA 125 for Immunotherapy of Ovarian Cancer

Abstract

A new concept of oncological immunotherapy comprises the attempt to trigger the immune system of the host into a response against tumor cells. Antiidiotypic antibodies bearing the internal image of an antigen expressed on the surface of the tumor seem to be most suited for this purpose. We have generated a murine antiidiotypic antibody (ACA 125) functionally imitating the tumor-associated antigen CA 125, which can be detected in about 80% of ovarian carcinomas. The hybridoma cell was adapted to serum-free medium and antibody was produced in a hollow fiber cell culture system (Technomouse). ACA 125 (Ab2) shows high affinity for the paratope of Ab1 (affinity constant: 2.3 x 10(9) liters/mol) and binding of Ab2 to Ab1 is completely inhibited by the nominal antigen. Application of F(ab')2 fragments of ACA 125 to rats lead to an anti-CA 125 immunity by production of IgG and IgM antiantiidiotypic antibodies (Ab3) that bind to both ACA 125 and CA 125. Furthermore the induction of a non-MHC-restricted cell-mediated cytotoxicity for human ovarian adenocarcinoma cell line NIH-OVCAR3 (expressing CA 125 on its surface) could be proved; additionally complement-dependent cytotoxicity (CDC) as well as an antibody-dependent cellular cytotoxicity (ADCC) was observed. Thus, monoclonal antiidiotypic antibody ACA 125 fulfills recent criteria for an antibody, which might be successful in immunotherapy using the anti-idiotypic network approach.

Cytotoxic activity of novel human monoclonal antibody MT201 against primary ovarian tumor cells

“…In vitro CDC as well as ADCC was observed by ACA 125, but further investigations in vivo Concentrations of MT201 and rituximab tested are indicated. Data are from a FACS-based cytotoxicity assay are necessary for determination of its efficacy (Schlebusch et al 1995). M0v18 is a chimeric monoclonal that binds the membrane folate receptor expressed on ovarian carcinoma cells.…”

Vaccination of Patients with Advanced Ovarian Carcinoma with the Anti-Idiotype ACA125

“…This antibody functionally imitates the CA125 antigen and induces humoral as well as cellular anti-CA125 immunity in animals (21,22) and humans (16,18,23). A clinical Phase I study in patients with recurrent ovarian carcinoma showed that 67% of the patients developed specific anti-anti-Id antibody (Ab3) directed against the vaccine.…”

Preparation of Humanized Ovarian Carcinoma Anti-Idiotypic Minibody

“…In a series of studies of Wagner, Anti-anti-Id antibodies (Ab 3 ) that bind to ACA125 (Ab 2 ) and CA125(Ab 1 ) were produced by application ACA125 to immune epithelial ovarian cancer or recurrences. (18)(19)(20)(21) Forty-two patients with platinum-pretreated recurrences were included in a clinical Phase I/II trial of consolidation in third-line therapy. The survival of the whole ACA125-treated collective of patients after a mean of 12.6 antibody applications was 14.9 6 12.9 months.…”