RNA viruses expressing IL-12 for immunovirotherapy
The present invention relates to a recombinant virus of the family Paramyxoviridae, comprising at least one expressible polynucleotide encoding an IL-12 polypeptide, wherein said IL-12 polypeptide is an IL-12 fusion polypeptide comprising a p35 subunit of an IL-12 and a p40 subunit of an IL-12; to a polynucleotide encoding the same, and to a kit comprising the same. Moreover, the present invention relates to a method for treating cancer in a subject afflicted with cancer, comprising contacting said subject with a recombinant virus of the family Paramyxoviridae of the invention, and thereby, treating cancer in a subject afflicted with cancer.
1. A recombinant virus of the family Paramyxoviridae comprising at least one expressible polynucleotide encoding an interleukin 12 (IL-12) polypeptide wherein said IL-12 polypeptide is a fusion protein comprising a p35 subunit of an IL-12 and a p40 subunit of an IL-12, wherein said polynucleotide optionally encodes a ligand for an immune checkpoint blockade protein or a binding domain to a tumor associated antigen, and wherein said recombinant virus is encoded by a polynucleotide comprising the nucleic acid sequence selected from the group consisting of SEQ ID NOS 4 to 7, 14 and 15.
2. A host cell comprising the recombinant virus of the family Paramyxoviridae according to claim 1 .
3. A medicament comprising
(a) (i) the recombinant virus of the family Paramyxoviridae according to claim 1 ; and/or
(a)(ii) a host cell comprising the recombinant virus of the family Paramyxoviridae according to claim 1 ; and
(b) at least one pharmacological acceptable excipient.
4. A method for treating cancer in a subject afflicted with cancer, comprising administering to said subject a therapeutically effective amount of the medicament according to claim 3 , thereby treating cancer in a subject afflicted with cancer.
5. The method of claim 4 , wherein said cancer is a solid cancer, a metastasis, or a relapse thereof.
6. The method of claim 4 , wherein treating cancer is reducing tumor burden.
7. The method of claim 4 , wherein said cancer is malignant melanoma, head and neck cancer, hepatocellular carcinoma, pancreatic carcinoma, prostate cancer, renal cell carcinoma, gastric carcinoma, colorectal carcinoma, lymphomas or leukemias.