Targeting of human interferon antagonists
The present invention relates to a fusion protein, comprising a cytokine antagonist and a targeting moiety, preferably an antibody or anti-body like molecule. In a preferred embodiment, the cytokine antagonist is a modified cytokine which binds to the receptor, but doesn't induce the receptor signalling. The invention relates further to a fusion protein according to the invention for use in treatment of cancer and immune- or inflammation-related disorders.
1. A composition comprising a fusion protein comprising an interferon antagonist and a targeting moiety, wherein: the interferon antagonist is a human IFNα2 comprising an R120E mutation which provides antagonism; and the targeting moiety comprises a variable domain of camelid heavy chain antibody (VHH) or a variable domain of new antigen receptor (VNAR) directed to CD20 which provides B cell-specific targeting of antagonistic activity.
2. The composition according to claim 1 , wherein the human IFNα2 comprises a second mutation that decreases binding activity of the interferon antagonist.
3. The composition according to claim 2 , wherein the second mutation is R149A.
4. A pharmaceutical composition comprising the composition according of claim 3 ; and a suitable excipient.
5. The composition of claim 3 , further comprising a linker, connecting the interferon antagonist and a targeting moiety.
6. A pharmaceutical composition comprising the composition according of claim 5 ; and a suitable excipient.
7. The composition according to claim 2 , wherein the second mutation is L153A.
8. A pharmaceutical composition comprising the composition according of claim 7 ; and a suitable excipient.
9. The composition of claim 7 , further comprising a linker, connecting the interferon antagonist and a targeting moiety.
10. A pharmaceutical composition comprising the composition according of claim 9 ; and a suitable excipient.
11. A pharmaceutical composition comprising the composition according of claim 1 ; and a suitable excipient.
12. The composition of claim 1 , further comprising a linker, connecting the interferon antagonist and a targeting moiety.
13. A pharmaceutical composition comprising the composition according of claim 12 ; and a suitable excipient.