A MONOCLONAL ANTIIDIOTYPIC ANTIBODY ACA-125 MIMICKING THE TUMOR-ASSOCIATED ANTIGEN CA-125 FOR IMMUNOTHERAPY OF OVARIAN-CANCER

A new concept of oncological immunotherapy comprises the attempt to tr igger the immune system of the host into a response against tumor cell s, Antiidiotypic antibodies bearing the internal image of an antigen e xpressed on the surface of the tumor seem to be most suited for this p urpose, We have generated a murine antiidiotypic antibody (ACA 125) fu nctionally imitating the tumor-associated antigen CA 125, which can be detected in about 80% of ovarian carcinomas, The hybridoma cell was a dapted to serum-free medium and antibody was produced in a hollow fibe r cell culture system (Technomouse). ACA 125 (Ab2) shows high affinity for the paratope of Abl (affinity constant: 2.3 x 10(9) liters/mol) a nd binding of Ab2 to Abl is completely inhibited by the nominal antige n, Application of F(ab')(2) fragments of ACA 125 to rats lead to an an ti-CA 125 immunity by production of IgG and IgM antiantudiotypic antib odies (Ab3) that bind to both ACA 125 and CA 125, Furthermore the indu ction of a non-MHC-restricted cell-mediated cytoxicity for human ovari an adenocarcinoma cell line NIH-OVCAR3 (expressing CA 125 on its surfa ce) could be proved; additionally complement-dependent cytotoxicity (C DC) as well as an antibody-dependent cellular cytotoxicity (ADCC) was observed, Thus, monoclonal antiidiotypic antibody ACA 125 fulfills rec ent criteria for an antibody, which might be successful in immunothera py using the anti-idiotypic network approach.