Human immune response to monoclonal antibody administration is dose-dependent

H. F. Sears, D. J. Bagli, D. Herlyn, E. DeFreitas, H. Suzuki, G. Steele and H. Koprowski
Department of Surgery, New England Deaconess Hospital, Boston, MA 02215.

When mouse monoclonal antibodies (MAbs) are injected into patients they usually induce an immune response. The resultant human anti-mouse-immunoglobulin antibody (Hu-aMAb) limits multiple injections of these reagents. A strategy to decrease the production of Hu-aMAb was tested in 20 patients with advanced gastrointestinal carcinoma. Ten patients received 700 mg of MAb as their initial exposure to mouse immunoglobulin, while the other ten patients received 100-mg of immunoglobulin initially. Each group received the same maintenance regimen until Hu-aMAb or disease progression was detected. Six patients in the high-dose group did not produce detectable Hu-aMAb for up to five months after initial exposure. All ten of the patients who received the low initial dose developed Hu-aMAb. Allergic reaction did not occur in the absence of Hu-aMAb. This larger initial dose in vivo injection strategy may allow repetitive exposure to MAb reagents without Hu-aMAb limiting further diagnostic or therapeutic use of murine immunoglobulin.