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 a cytokine, which is IFNγ, and a peptide containing the NGR motif.
2. A conjugation product between IFNγ and a peptide containing the NGR motif, wherein said peptide is selected from the group consisting of 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), and cyclic CNGRC (SEQ ID NO: 12).
3. A conjugation product as claimed in claim 2 , wherein the cytokine is derivatized with polyethylene glycol or an acyl residue.
4. A conjugation product as claimed in claim 3 , wherein the cytokine is further conjugated with an antibody, or a fragment thereof, directed to a tumoral antigen, a tumoral angiogenic marker, a component of the extracellular matrix, or with biotin.
5. A cDNA encoding for IFN γ bearing a 5′ or 3′ contiguous sequence encoding a peptide containing the NGR motif.
6. A cDNA according to claim 5 , wherein said peptide is a peptide selected from the group consisting of CNGRCVSGCAGRC (SEQ IN NO: 8), NGRAHA (SEQ ID NO: 9), GNGRG (SEQ ID NO: 10), cycloCVLNGRMEC (SEQ IN NO: 11), linear CNGRC (SEQ IN NO:13), and cyclic CNGRC (SEQ ID NO:12).
7. A pharmaceutical composition comprising an effective amount of a conjugation product as claimed in claim 1 , together with at least one pharmaceutically acceptable carrier, excipient, or a combination thereof.
8. A composition as claimed in claim 7 , in the form of an injectable solution or suspension or a liquid for infusions.
9. A composition as claimed in claim 7 , in the form of liposomes.
10. A conjugation product as claimed in claim 1 wherein the cytokine is linked to the peptide through a spacer.
11. A conjugation product as claimed in claim 2 wherein the cytokine is linked to the peptide through a spacer.
12. A conjugation product as claimed in claim 2 wherein said peptide is linear or cyclic CNGRC (SEQ ID NOs: 13 and 12, respectively) and wherein said peptide is linked to the cytokine through the spacer G.
13. A cDNA encoding a conjugation product as defined in claim 10 .
14. A cDNA encoding a conjugation product as defined in claim 11 .
15. A cDNA encoding a conjugation product as defined in claim 12 .
16. The conjugation product according to claim 1 , wherein the cytokine is linked to the N-terminus of the peptide through the spacer G.
17. The conjugation product according to claim 2 , wherein the peptide is linear or cyclic CNGRC (SEQ ID NOs: 13 and 12, respectively) and wherein IFNγ is linked to the N-terminus of the peptide through the spacer G.