Type I and type III interferon fusion molecules and methods for use thereof
Fusion molecules composed of a type I interferon protein or portion thereof and a type III interferon protein or portion thereof, pharmaceutical compositions containing the fusion molecules, and methods for their use in inhibiting infection, inhibiting or treating cancer, inducing signaling of transcription of IFN-stimulated genes through an IFN-αR2 chain in a subject suffering from an infection which degrades or downregulates an IFN-αR1 chain, and treating various diseases or conditions are provided.
1. A fusion molecule comprising a human type I interferon protein selected from interferon alpha or interferon beta or a fragment shorter in length than the full length interferon protein and which maintains at least a portion of functional activity of the full length protein and/or binding to at least one of the receptor subunits, a human type III interferon protein selected from interferon lambda 1, interferon lambda 2 or interferon lambda 3 or a fragment shorter in length than the full length interferon protein and which maintains at least a portion of the functional activity of the full length protein and/or binding to at least one of the receptor subunits and a linker selected from SEQ ID NO:23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 between the human type I interferon protein or fragment thereof and human type III interferon protein or fragment thereof.
2. The fusion molecule of claim 1 , wherein the human type I interferon protein or fragment thereof is human interferon alpha or a fragment thereof.
3. The fusion molecule of claim 2 , wherein the human interferon alpha or fragment thereof is human interferon alpha 2 or a fragment thereof.
4. The fusion molecule of claim 1 , wherein the human type I interferon protein or fragment thereof is human interferon beta or a fragment thereof.
5. The fusion molecule of claim 1 , wherein the human type III interferon protein or fragment thereof is human interferon lambda 1 or a fragment thereof.
6. The fusion molecule of claim 1 , wherein the human type III interferon protein or fragment thereof is human interferon lambda 2 or a fragment thereof.
7. The fusion molecule of claim 1 , wherein the human type III interferon protein or fragment thereof is human interferon lambda 3 or a fragment thereof.
8. The fusion molecule of claim 1 further comprising a signal peptide at its N-terminus.
9. The fusion molecule of claim 1 comprising a mature portion of the human type I interferon protein or the human type III interferon protein.
10. The fusion molecule of claim 1 comprising an entire sequence inclusive of a signal peptide of the human type I interferon protein or the human type III interferon protein.
11. A pharmaceutical composition comprising the fusion molecule of claim 1 and a pharmaceutically acceptable carrier.
12. A method for treating a disease or condition in a subject, said method comprising administering to the subject an effective amount of the fusion molecule of claim 1 thereby treating the subject's disease or condition, wherein the disease or condition is a viral infection, a fungal infection, a bacterial infection, cancer, an inflammatory disease, or an autoimmune disease.