Modification of human leukocyte interferon pharmacology with a monoclonal antibody.
The antitumor and antiviral properties of the interferons have been well established. However, the usefulness of the interferons may be limited, in part, because of rapid clearance from the plasma and degradation by plasma or tissue enzymes. A monoclonal antibody (IFG-252.2) was developed which binds to recombinant DNA-produced human alpha-interferon (rIFN-alpha A) without measurably reducing its in vitro antiviral or antiproliferative properties. Pharmacokinetic studies of rIFN-alpha A:antibody complex in the intact, anesthetized rat showed that rIFN-alpha A activity cleared from plasma 3-fold slower than found after injection of free rIFN-alpha A. This resulted in a 15-fold increase in its calculated area under concentration curve compared to that of free rIFN-alpha A. These studies suggest that interferon bound to a monoclonal antibody may provide a means to prevent the normal clearance and degradation of free interferon and may result in prolonged antitumor and antiviral plasma activity in vivo. Furthermore, it suggests that monoclonal antibodies to various biologically active agents may be used to favorably alter their pharmacokinetics while leaving their biological activity unaltered.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D007370:Interferon Type I