Quantitation of mouse monoclonal antibody and human anti-mouse antibody response in serum of patients.

The assays required to study pharmacokinetics of monoclonal antibodies and human anti-mouse antibody response in man, utilizing enzyme linked immunosorbent assay, have been at best semi-quantitative. We have developed and well characterized a quantitative assay for measurement of murine monoclonal antibodies and human anti-mouse antibody in circulation of patients injected with murine monoclonal antibodies. The sensitivity of mouse IgG assay is approximately 1 ng/ml and cross reactivity of IgG's from other species were less than 0.01%. The pre-therapy samples from 30 patients treated with monoclonal antibody CO17-1A as well as serum from 54 individuals had no detectable human anti-mouse antibody indicating specificity. The sensitivity of this assay was approximately 10 mg/ml. The utility of these assays was demonstrated in a group of patients receiving 400 mg of monoclonal antibody CO17-1A. The half-life and the degree of immune response can be measured using these assays.