In vivo effects of murine hybridoma monoclonal antibody in a patient with T-cell leukemia

Abstract

Abstract A murine monoclonal antibody directed against a normal T-cell differentiation antigen was given to a patient with adult T-cell leukemia. Immunofluorescence staining showed increased amounts of this antigen on the patient's leukemia cells. Using a competition radioimmunoassay, free antigen was not detectable in the serum prior to therapy. Two courses of in vivo therapy were given using a 1-mg dose. Each produced a prompt and dramatic fall in WBC with return to pretreatment levels over the ensuing 24 hr, a pattern similar to that seen with leukopheresis. After the first dose of antibody, circulating free antigen became detectable in the serum and a transient decline in creatinine clearance was noted. A 5-mg dose of antibody given at that time was ineffective, presumably because it was blocked by free antigen. Antigenic modulation by leukemia cells was found transiently following each course of antibody. A weak and clinically insignificant host antimouse antibody response was found 5 days after the first treatment. The patient tolerated antibody therapy without difficulty. Monoclonal antibodies offer promise as an immunotherapeutic approach to cancer but problems encountered here must be addressed.