Targeted human-interferon fusion proteins
This disclosure relates to a modified α-helical bundle cytokine, with reduced activity via an α-helical bundle cytokine receptor, wherein the α-helical bundle cytokine is specifically delivered to target cells. Preferably, the α-helical bundle cytokine is a mutant, more preferably it is a mutant interferon, with low affinity to the interferon receptor, wherein the mutant interferon is specifically delivered to target cells. The targeting is realized by fusion of the modified α-helical bundle cytokine to a targeting moiety, preferably an antibody. This disclosure relates further to the use of such targeted modified α-helical bundle cytokine to treat diseases. A preferred embodiment is the use of a targeted mutant interferon, to treat diseases, preferably viral diseases and tumors.
1. A composition comprising a targeting construct, the targeting construct comprising: mutated human interferon alpha 2, said mutated human interferon alpha 2 having a R149A mutation and a reduced affinity as compared to the wild type human interferon alpha 2, and a targeting moiety, said targeting moiety comprises an antibody directed to a programmed death-ligand 2 (PD-L2), wherein the targeting moiety restores the reduced affinity of the mutated human interferon alpha 2 for IFNAR2 on targeted cells.
2. The targeting construct according to claim 1 , wherein said antibody is a nanobody.
3. A pharmaceutical composition comprising a targeting construct, the targeting construct comprising:
the composition according of claim 1 ; and
a suitable excipient.
4. The composition of claim 1 , further comprising a linker
wherein the mutated human interferon alpha 2 and the targeting moiety are connected via a linker.