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Modification of Human Leukocyte Interferon Pharmacology with a Monoclonal Antibody¹

Department of Clinical Immunology and Biological Therapy, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030 [M. G. R., J. U. G., E. M. H.], and Hybritech Inc., San Diego, California 92121 [B. W. U., G. S. D., J. M. F.]

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 -interferon (rIFN-A) without measurably reducing its in vitro antiviral or antiproliferative properties. Pharmacokinetic studies of rIFN-A:antibody complex in the intact, anesthetized rat showed that rIFN-A activity cleared from plasma 3-fold slower than found after injection of free rIFN-A. This resulted in a 15-fold increase in its calculated area under concentration curve compared to that of free rIFN-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 biological active agents may be used to favorably alter their pharmacokinetics while leaving their biological activity unaltered.

¹ This work was supported in part by a grant from Hybritech, Inc. Research was conducted, in part, by the John D. and Catherine T. MacArthur Foundation, the Clayton Foundation for Research, and the James E. Lyon Foundation for Research.

² To whom requests for reprints should be addressed, at Department of Clinical Immunology and Biological Therapy, Box 41, M. D. Anderson Hospital and Tumor Institute, 6723 Bertner Avenue, Houston, TX 77030.

³ Senior Clayton Foundation investigator.

Received 12/26/84. Revised 2/25/85. Accepted 3/ 6/85.

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