Recombinant oncolytic newcastle disease viruses with increased activity

A recombinant Newcastle Disease Virus (NDV), carrying as a foreign gene at least one gene selected from the group consisting of:

• a gene encoding an antibody directed to the surface protein CTLA-4 or an antigen-binding part thereof directed to the surface protein CTLA-4 (anti-CTLA-4), such as Ipilimumab, an antigen-binding part of Ipilimumab, a functional analog of Ipilimumab or a functional analog of an antigen-binding part of Ipilimumab,
• a gene encoding a protein which improves the cellular immune response and improves the ability of T cells to enter tumor cells, or a part thereof which improves the cellular immune response and improves the ability of T cells to enter tumor cells, such as interleukin-12 (IL-12), a part of interleukin-12, a functional analog of interleukin-12 or a functional analog of a part of interleukin-12,
• a gene encoding a protein with the ability to modulate the virus replication cycle, or a part thereof with the ability to modulate the virus replication cycle, such as the non-structural protein NS1 of influenza A virus, a part of the non-structural protein NS1 of influenza A virus, a functional analog of the non-structural protein NS1 of influenza A virus or a functional analog of a part of the non-structural protein NS1 of influenza A virus, and
• any combination of these genes, parts or funcational analogs thereof, wherein
• said recombinant NDV having a mutation in the HN gene leading to a change in the amino acid sequence of the respective gene product and providing the NDV with an increased replication capability in a human cancer cell as compared to an otherwise identical NDV not having the said mutation in the HN gene, preferably allowing replication of said NDV in a human cancer cell in an at least 2-fold higher level.