Activating anti‐idiotypic human anti‐mouse antibodies for immunotherapy of ovarian carcinoma

• Published in: Cancer Vol. 73; no. S3; pp. 1121 - 1125
• Main Authors: Baum, R. P., Niesen, A., Hertel, A., Nancy, A., Hess, H., Donnerstag, B., Sykes, T. R., Sykes, C. J., Suresh, M. R., Noujaim, A. A., Hör, G.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.02.1994; Wiley-Liss
• Subjects: Animals; Antibodies, Anti-Idiotypic - therapeutic use; Antibodies, Monoclonal - therapeutic use; Antigens, Tumor-Associated, Carbohydrate - immunology; Antigens, Tumor-Associated, Carbohydrate - metabolism; Antineoplastic agents; anti‐idiotypic human anti‐mouse antibodies; Biological and medical sciences; Female; HAMA; Humans; Immunotherapy; Medical sciences; Mice - immunology; monoclonal antibody; ovarian carcinoma; Ovarian Neoplasms - therapy; Pharmacology. Drug treatments; Radioimmunotherapy - methods
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/1097-0142(19940201)73:3+<1121::AID-CNCR2820731353>3.0.CO;2-Q

Human anti‐mouse antibodies (HAMA) are observed frequently after immunoscintigraphy with monoclonal antibodies (MoAb) directed against CA‐125.1 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 immunoscintigraphy). 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 to a significant HAMA increase. The use of different assays, or HAMA removal before in vitro testing, can solve this problem. After a new CA‐125 assay containing antibodies that recognize different epitopes on the CA‐125 antigen (Biomira Tru‐Quant OV) was applied, only mildly increased assay results or normal levels were measured. Most of HAMA‐positive patients demonstrated a predominantly anti‐idiotypic response, determined with two different HAMA assays. Seven patients with anti‐idiotypic HAMA responses after OC‐125 immunoscintigraphy remained free of tumor 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 Index > 70%) and show no significant tumor progression. In light of their extremely poor prognoses (5‐year survival rates of 3–5% in recurrent International Federation of Gynecology and Obstetrics III/IV stages), without further chemotherapy, these courses are extremely unusual. Preliminary in vitro experiments lead to the postulatation that anti‐idiotypic HAMA may trigger an antitumor effect either by suppressing the growth of CA‐125‐expressing cancer cells directly, or by activating the patient's immune response via induction of Ab3. Similar results are observed after immunoscintigraphy with a technetium‐99m‐labeled anti‐CA‐125 monoclonal antibody (B43.13), which the authors now also use for immunotherapy 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.