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.
In the follow-up of ovarian cancer patients, rising levels of the tumor-associated antigen CA 125 are an indication for immunoscintigraphy. Human anti-mouse antibodies (HAMA) are frequently found after immunoscintigraphy with murine MAb directed against CA 125. Since we observed that patients developing high HAMA-levels in serum remained free of tumor or had stable disease, we examined the cytotoxic activity of peripheral blood lymphocytes (PBL) by a fluorescence-based assay. Our results demonstrate that PBLs of patients with high anti-idiotypic antibodies show an increased cytotoxic activity (by a factor of 4) compared to those of patients with low HAMA levels. The clinical course of the patients after the first injection of murine monoclonal antibody was observed over a period of 1 to 3 years. Improvement or deterioration of patients' clinical condition corresponded with the results obtained by functional analysis. Further investigations concerning the course of cytotoxic activity in HAMA-positive patients will have to clarify HAMA's role in the immune response.
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