| abstract |
Disclosed are cytokines which are site-specifically mutated to have one unpaired cysteine residue located apart from the receptor-binding site, and conjugates thereof, in particular, conjugates where a lipophilic group is conjugated to the unpaired cysteine residue, and to such conjugates of cytokines which have an unpaired cysteine residue located apart from the receptor-binding site in the native form. All of these cytokines are of the type such that conjugation of a lipophilic group to the unpaired cysteine residue does not significantly affect the receptor binding or biological acitivity of the conjugated product. Also disclosed are conjugates where a lipophilic group, an antibody, horseradish peroxidase, alkaline phosphatase, fluorescein substances, biotin, or a cytotoxin is conjugated to the unpaired cysteine residue. These fatty acyl conjugated cytokines penetrate better and are retained longer in local sites and can be locally administered to treat, e.g., solid tumors, spinal injuries, the external genital area, the throat, ears, nasal linings, eyes, and skin. |