Anti-TAG-72 Antibody B72.3—Immunological and Clinical Effects in Ovarian Carcinoma

Abstract

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 (Ab2β) 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.