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 method of treating or diagnosing a cancer patient comprising administering simultaneously, sequentially or separately: (a) an effective amount of a conjugation product of TNF and a ligand of the CD13 receptor, wherein the ligand is a peptide comprising the NGR motif, and (b) an effective amount of IFNγ.
2. The method as claimed in claim 1 , wherein said TNF is TNFα or TNFβ.
3. The method as claimed in claim 1 , wherein said peptide comprises a sequence selected from the group consisting of CNGRCVSGCAGRC (SEQ ID NO:1), NGRAHA (SEQ ID NO:2), GNGRG (SEQ ID NO:3), CNGRCG (SEQ ID NO:18), cycloCVLNGRMEC (SEQ ID NO:4), linear CNGRC (SEQ ID NO:5), and cyclic CNGRC (SEQ ID NO:6).
4. The method as claimed in claim 3 , wherein the TNF is linked to the peptide through a spacer.
5. The method as claimed in claim 3 , wherein the conjugation product is between TNF and linear or cyclic CNGRC and wherein the amino-terminal of TNF is linked to the peptide through the spacer G.
6. The method as claimed in claim 1 , wherein the TNF is derivatized with polyethylene glycol or an acyl residue.
7. The method as claimed in claim 1 , wherein the TNF is further conjugated with an antibody or fragment thereof, 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.
8. The method according to claim 7 , wherein the TNF is conjugated to both a peptide comprising the NGR motif and an antibody or fragment thereof on different subunits.
9. The method as claimed in claim 1 , wherein the conjugation product of TNF and the peptide comprising the NGR motif and the IFNγ are in the form of an injectable solution or suspension or a liquid for infusion.
10. The method as claimed in claim 1 , wherein the conjugation product of TNF and the peptide comprising the NGR motif and the IFNγ are in the form of liposomes.
11. The method of claim 1 comprising additionally administering other antitumor agents or diagnostic tumor-imaging compounds.