Human anti-mouse antibody suppression with cyclosporin A

Cyclosporin was used in an attempt to suppress the formation of human antimouse antibody (HAMA) after administration of murine monoclonal antibodies.

Thirteen patients were given oral cyclosporin (8.6-15 mg/kg/day) starting 2 days before administration of technetium-99m (99mTc) labeled F(ab')2 (3 patients) or Fab (10 patients) murine antibody fragment. Six to nine days later, patients received either rhenium-186 (186Re)-labeled F(ab')2 or an intact antibody. Cyclosporin was continued for 14 days after the second antibody administration.

Five patients (38%) did not develop elevated HAMA titers for up to 8 weeks after antibody administration. These five patients had a median cyclosporin concentration of 726 ng/ml, while the eight patients who developed HAMA had a median cyclosporin level of 364 ng/ml. In contrast, when not given cyclosporin, 86% (24/28) of patients developed HAMA after receiving two doses of F(ab')2, and 100% (15/15) developed HAMA after receiving Fab followed by intact antibody. Toxicity from cyclosporin included elevation concentrations of bilirubin and creatinine, and increased blood pressure, which rapidly resolved after the cyclosporin was discontinued.

This study demonstrates that cyclosporin given from 2 days before until 2 weeks after administration of either a F(ab')2 or intact murine antibody can suppress HAMA formation. This strategy may permit administration of repeated doses of murine-antibody-based radioimmunotherapy.