Modified cytokines for use in cancer therapy
View Patent ↗Cytokine derivatives capable of homing the tumoral vessels and the antigen presenting cells and the use thereof as antitumoral agents.
1. A conjugation product between TNF and a peptide containing the NGR motif, wherein said peptide comprises CNGRCVSGCAGRC (SEQ ID NO: 8), NGRAHA (SEQ ID NO: 9), GNGRG (SEQ ID NO: 10), cycloCVLNGRMEC (SEQ ID NO: 11), linear CNGRC (SEQ ID NO: 13), or cyclic CNGRC (SEQ ID NO: 12), and
wherein said peptide is 5–100 amino acids in length.
2. A conjugation product as claimed in claim 1 , wherein said TNF is TNFα or TNFβ.
3. A conjugation product as claimed in claim 1 , wherein said peptide is selected from the group consisting of linear CNGRC (SEQ ID NO: 13) and cyclic CNGRC (SEQ ID NO: 12).
4. A conjugation product as claimed in claim 1 , wherein the TNF is derivatized with polyethylene glycol or an acyl residue.
5. A conjugation product as claimed in claim 1 , wherein the TNF is further conjugated with a compound selected from the group consisting of an antibody, an antibody fragment, and biotin, wherein said antibody or fragment thereof is directed to a compound selected from the group consisting of a tumoral antigen, a tumoral angiogenic marker and a component of the extracellular matrix.
6. Pharmaceutical composition comprising an effective amount of a conjugation product as claimed in claim 1 , together with pharmaceutically acceptable carriers and excipients.
7. A composition as claimed in claim 6 , in the form of an injectable solution or suspension or a liquid for infusions.
8. A composition as claimed in claim 6 , in the form of liposomes.
9. A method of treating a patient having a tumor that expresses CD13 in angiogenic endothelium, comprising administering the conjugation product of claim 1 to said patient.
10. The method of claim 9 , comprising additionally administering other antitumor agents.
11. The method of claim 9 , wherein said patient has lymphoma or melanoma.