Anti-TAG-72 antibody B72.3--immunological and clinical effects in ovarian carcinoma.
Based on the network theory, anti-tumor antibodies (Ab1) can trigger the immune system of the host into a response against tumor cells. Through an immunological cascade, anti-idiotypic antibodies bearing the internal image of epitopes of the nominal antigen (Ab2 beta) are produced that themselves can induce cellular and humoral cytotoxic effects against the antigen-expressing tumor cell. Formation of such antibodies has been shown to be associated with prolonged survival of melanoma, colorectal, and ovarian carcinoma patients. We studied anti-idiotypic antibody (Ab2) responses and clinical outcome of 31 ovarian cancer patients receiving the monoclonal antibody (MAb) B72.3, which targets the ovarian carcinoma associated antigen TAG-72. All patients were treated by surgery and polychemotherapy, which was followed by repeated (mean of 4) injections of 1 mg of the MAb B72.3. A remarkable anti-idiotypic anti-B72.3 response arose in 19 patients, with 9 of them showing a major response with Ab2 serum concentrations greater than 1,000 U/ml ("high-responders"). The median disease-free survival time, as well as the median survival time of these high-responders, was increased as compared to the low- or no responders. Evaluating our data, we conclude that monoclonal antibody treatment with the MAb B72.3 may induce humoral immunological responses in about two-thirds of our study group, although a positive clinical effect may only be expected in patients with excessive anti-idiotypic antibody formation.
Schmolling
J
J
Department of Obstetrics and Gynecology, University of Bonn, Germany.
Reinsberg
J
J
Wagner
U
U
Krebs
D
D
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology* / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D051379:Mice; D008875:Middle Aged; D008958:Models, Molecular; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000628:therapy
D000888:Antibodies, Anti-Idiotypic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C091202:B72.3 antibody; D006023:Glycoproteins; C047052:tumor-associated antigen 72