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Antiidiotype Antibodies in Cancer Patients Receiving Monoclonal Antibody to Carcinoembryonic Antigen¹

Center for Molecular Medicine and Immunology [F. J. P., D. M. G.] and Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, [U. C. T., R. D. J., M. L., D. M. G.], Newark, New Jersey 07103

The initial 10 patients of a Phase I clinical trial involving multiple injections of murine monoclonal anti-carcinoembryonic antigen (CEA) antibody, NP-2, were studied for the presence in their sera of antiidiotypic antibody. Most patients had advanced gastrointestinal adenocarcinoma and received 1 mg/m² monoclonal antibody three times weekly, or once a week, resulting in five to 13 injections over 12 to 240 days. Antiidiotype antibody was detected with a blocking radioimmunoassay using [¹²⁵I]NP-2-F(ab')₂ binding to CEA-coated microwells and [¹²⁵I]NP-4-F(ab')₂ as a control antibody. Five out of 10 patients demonstrated 65–96% inhibition of NP-2 binding at 1/20 dilution of serum compared to NP-2 binding in the presence of pretreatment sera. The inhibitory activity was preserved after adsorption over a polyclonal mouse IgG immunoadsorbent whereas exposure to a NP-2 affinity column completely depleted the activity. Specificity testing, including the blocking effect of patient sera on the control antibody NP-4, and interference by the possible presence of circulating NP-2, circulating CEA, and human anti-CEA activity, confirmed that the inhibition observed was specific for NP-2 and was caused by an agent with CEA-like characteristics. Longitudinal studies demonstrated that elevated titers of antiidiotypic antibody appeared later in the course of immunization than did antibody against mouse immunoglobulin. These studies indicate that patients can be sensitized to the idiotype (anti-combining site and/or combining site-related) of monoclonal antibodies to CEA following multiple infusions.

¹ Supported in part by NIH Grant CA-39841 and by New Jersey Medical School Research Foundation Grant 18–86.

² To whom requests for reprints should be addressed, at Center for Molecular Medicine and Immunology, 1 Bruce Street, Newark, NJ 07103.

Received 8/10/87. Revised 1/14/88. Revised 4/11/88. Accepted 4/14/88.

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