abstract |
Cytokines are described whose specific sites are mutated so as to present an unpaired cysteine residue placed outside the receptor binding site. Their conjugates are also described, in particular those in which a lipophilic group conjugates with the unpaired cysteine residue and with cytokine conjugates having an unpaired cysteine residue placed outside the receptor binding site in their original form. All these cytokines are of a type such that the conjugation of a lipophilic group with the unpaired cysteine residue does not significantly disturb the binding of the receptor or the biological activity of the conjugated product. Also described are conjugates where a lipophilic group, an antibody, horseradish peroxidase, alkaline phosphatase, substances derived from flurescine, biotin or a cytotoxin conjugate with the unpaired cysteine residue. These cytokines conjugated with fatty acyls penetrate better and remain longer in local sites and can be administered locally to treat for example solid tumors, injuries of the spine, the external genital area, throat, nose, nasal mucous membranes, eyes and skin. |