Delivery of Interferons to Target Cells by Monoclonal Antibodies: Potential for the Specific Targeting of Other Lymphokines

Abstract

The successful cloning, production and purification of interferons (IFN) and other lymphokines (LKs) have revived interest in their therapeutic potential as both antitumor and immunomodulatory molecules. However, clinical studies with conventionally administered IFNs have produced ambiguous results. It was soon realized that both natural and recombinant IFNs have a very short half-life and at higher doses produced severe side effects. This is not surprising, because LKs are induced and probably also produced locally, released into microenviroments and they mostly act on neighboring cells (1). All the IFNs which are of about 20 Kd molecular weight act through their specific cell surface receptors. Since various kinds of cells in the body bear IFN receptors and almost all IFNs exert multiple biological activities, natural target cell specificity of IFNs is considered to be very limited. Consequently, systemically administered IFNs can be expected to produce unwanted side effects with only little therapeutic benefit because of inefficient and improper body distribution. All this necessitates novel approaches for the clinical application of IFN or other LKs (2, 3, 4). One possible approach to overcome the above problems would be to deliver IFN to desired sites by antibodies (5, 6).