ACTIVATING ANTIIDIOTYPIC HUMAN ANTI-MOUSE ANTIBODIES FOR IMMUNOTHERAPY OF OVARIAN-CARCINOMA

Human anti-mouse antibodies (HAMA) are observed frequently after immun oscintigraphy with monoclonal antibodies (MoAb) directed against CA-12 5.(1) As the authors have shown previously,(2-5) HAMA can cause false- positive CA-125 values in routine CA-125 immunoradiometric assay (IRMA ) tumor-marker assays (in one case, up to 900 days after immunoscintig raphy). In 32 patients, the authors found a HAMA frequency of 34% (11/ 32: 3/7 after the first administration, 6/13 after the second, and 2/2 after the third). Ten patients developed extremely high CA-125 levels after undergoing the CIS IRMA assay (up to 80,000 U/ml) in parallel t o a significant HAMA increase. The use of different assays, or HAMA re moval before in vitro testing, can solve this problem. After a new CA- 125 assay containing antibodies that recognize different epitopes on t he CA-125 antigen (Biomira TruQuant OV) was applied, only mildly incre ased assay results or normal levels were measured. Most of HAMA-positi ve patients demonstrated a predominantly antiidiotypic response, deter mined with two different HAMA assays. Seven patients with anti-idiotyp ic HAMA responses after OC-125 immunoscintigraphy remained free of tum or or had stable disease (2-42 or more months), contrary to their poor prognoses that had been made based on the underlying stages of their tumors. All of these patients are currently doing well (Karnofsky Inde x > 70%) and show no significant tumor progression. In light oftheir e xtremely poor prognoses (5-year survival rates of 3-5% in recurrent In ternational Federation of Gynecology and Obstetrics III/IV stages), wi thout further chemotherapy, these courses are extremely unusual. Preli minary in vitro experiments lead to the postulatation that anti-idioty pic HAMA may trigger an antitumor effect either by suppressing the gro wth of CA-125-expressing cancer cells directly, or by activating the p atient's immune response via induction of Ab3. Similar results are obs erved after immunoscintigraphy with a technetium-99m-labeled anti-CA-1 25 monoclonal antibody (B43.13), which the authors now also use for im munotherapy of ovarian cancer patients by repeated injections, hoping that induction of anti-idiotypic HAMA will be beneficial for prolonged survival of patients with ovarian carcinoma. Cancer 1994; 73:1121-5.