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 ate disclosed.
1. A pharmaceutical composition comprising (a) an effective amount of a conjugation product of TNF and a peptide or polypeptide containing the NGR motif, or a polynucleotide encoding therefor, and (b) an effective amount of IFNγ or a polynucleotide encoding therefor, wherein said peptide or polypeptide containing the NGR motif comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6.
2. A composition according to claim 1 together with pharmaceutically acceptable carriers and excipients.
3. A composition as claimed in claim 1 , wherein said TNF is TNFα or TNFβ.
4. A composition as claimed in claim 1 , wherein the TNF is derivatized with polyethylene glycol or an acyl residue.
5. A composition 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. A composition according to claim 5 , wherein the TNF is conjugated to both a peptide or polypeptide containing the NGR motif and a compound selected from the group consisting of an antibody, an antibody fragment, and biotin.
7. A composition as claimed in claim 1 , in the form of an injectable solution or suspension or a liquid for infusions.
8. A composition as claimed in claim 1 , in the form of liposomes.
9. A composition as claimed in claim 1 , further comprising another antitumor agent or a diagnostic tumor-imaging compound.
10. A composition as claimed in claim 9 , wherein the another antitumor agent is doxorubicin.