Mammalian subjects having a neoplasm are treated with a virus and a camptothecin compound, for example irinotecan or topotecan. The virus is selected from the group consisting of a Newcastle disease virus, a measles virus, a vesicular stomatitis virus, an influenza virus, a Sindbis virus, a picornavirus, and a myxoma virus. The treatment can also include administration of a monoclonal antibody against epidermal growth factor receptor, for example cetuximab.

A recombinant fusion protein is disclosed. The fusion protein comprises: (a) a CD55 peptide sequence, (b) a linker sequence C-terminal to the CD55 sequence, (c) a transmembrane domain C-terminal to the linker sequence, and (d) an intracellular domain C-terminal to the transmembrane domain. The fusion protein does not contain a GPI anchor. The fusion protein can be expressed with an N-terminal secretory signal peptide, which is cleaved to yield the mature protein on the surface of a cell line or an enveloped virus. An oncolytic virus expressing the fusion protein is resistant to complement inactivation and can be used to treat cancer.

Provided are an oncolytic virus for treating brain tumors using a recombinant Newcastle disease virus into which a Newcastle disease virus (NDV) vector-based PTEN (phosphatase and tensin homolog) gene is inserted and a composition for treating brain tumors using the same which can be used for a therapeutic viral agent that can induce reduction of clinical symptoms or partial or complete remission through brain tumor cell death or brain tumor tissue reduction by expressing normal PTEN protein after being infected with brain tumor cells, as a recombinant Newcastle disease virus containing a human PTEN protein gene.

In one aspect, provided herein are naturally occurring and recombinantly produced avian paramyxovirus (APMV) (e.g., an APMV-2, APMV-3, APMV-4, APMV-6, APMV-7, APMV-8, and APMV-9 strain) and uses of such APMV for the treatment of cancer. In particular, provided herein are methods for treating cancer comprising administering a naturally occurring or recombinantly produced APMV-4 strain to a subject in need thereof. In another aspect, provided herein are recombinant APMV comprising a packaged genome, wherein the packaged genome comprises a transgene. In particular, described herein are recombinant APMV (e g., APMV-2, APMV-3, APMV-4, APMV-6, APMV-7, APMV-8, and APMV-9). In another aspect, provided herein are methods for treating cancer comprising administering a recombinant APMV (e g., APMV-2, APMV-3, APMV-4, APMV-6, APMV-7, APMV-8, and APMV-9) to a subject in need thereof, wherein the recombinant APMV comprises a packaged genome comprising a transgene. In particular, provided herein are methods for treating cancer comprising administering a recombinant APMV-4 to a subject in need thereof, wherein the recombinant APMV-4 comprises a packaged genome comprising a transgene. In specific aspects, the use of APMV serotypes other than APMV-1 (such as described herein, in particular AMPV-4) to treat cancer is based, in part, on the similar or enhanced in vivo anti-tumor activities when compared to oncolytic NDV La Sota-L289A strain.

A recombinant fusion protein is disclosed. The fusion protein comprises: (a) a CD55 peptide sequence, (b) a linker sequence C-terminal to the CD55 sequence, (c) a transmembrane domain C-terminal to the linker sequence, and (d) an intracellular domain C-terminal to the transmembrane domain. The fusion protein does not contain a GPI anchor. The fusion protein can be expressed with an N-terminal secretory signal peptide, which is cleaved to yield the mature protein on the surface of a cell line or an enveloped virus. An oncolytic virus expressing the fusion protein is resistant to complement inactivation and can be used to treat cancer.

The invention relates to Newcastle Disease Vims (NDV), an avian paramyxovirus, which has been demonstrated to possess significant oncolytic activity against mammalian cancers. The invention provides the elucidation of the mechanisms of NDV-mediated oncolysis as well as the development of novel oncolytic viruses through the use of genetic engineering. The invention also provides a nucleic acid encoding a reverse genetically engineered (rg-)NDV having a mutation in the HN gene, said mutation allowing replication of said rgNDV in a cancer cell to a higher level than replication of an otherwise identical rgNDV not having said mutation in the HN gene.

In one aspect, provided herein are naturally occurring and recombinantly produced avian paramyxovirus (APMV) (e.g., an APMV-2, APMV-3, APMV-4, APMV-6, APMV-7, APMV-8, and APMV-9 strain) and uses of such APMV for the treatment of cancer. In particular, provided herein are methods for treating cancer comprising administering a naturally occurring or recombinantly produced APMV-4 strain to a subject in need thereof. In another aspect, provided herein are recombinant APMV comprising a packaged genome, wherein the packaged genome comprises a transgene. In particular, described herein are recombinant APMV (e g., APMV-2, APMV-3, APMV-4, APMV-6, APMV-7, APMV-8, and APMV-9). In another aspect, provided herein are methods for treating cancer comprising administering a recombinant APMV (e g., APMV-2, APMV-3, APMV-4, APMV-6, APMV-7, APMV-8, and APMV-9) to a subject in need thereof, wherein the recombinant APMV comprises a packaged genome comprising a transgene. In particular, provided herein are methods for treating cancer comprising administering a recombinant APMV-4 to a subject in need thereof, wherein the recombinant APMV-4 comprises a packaged genome comprising a transgene. In specific aspects, the use of APMV serotypes other than APMV-1 (such as described herein, in particular AMPV-4) to treat cancer is based, in part, on the similar or enhanced in vivo anti-tumor activities when compared to oncolytic NDV La Sota-L289A strain.

The present invention provides methods for inducing regression of tumors in human subjects, the methods utilize a modified mesogenic strain of Newcastle disease virus (NDV) with modified F protein cleavage site, which is non-pathogenic to poultry (lentogenic), but exhibits oncolytic properties. The disclosed methods provide safe, effective and reliable means to induce regression of a tumor in an individual in need thereof. These methods overcome the drawbacks of using pathogenic strains of viruses for human therapy.

Described herein are chimeric Newcastle disease viruses comprising a packaged genome comprising a transgene encoding interleukin-12. The chimeric Newcastle disease viruses and compositions thereof are useful in combination with an antagonist of programmed cell death protein 1 (PD-1) or a ligand thereof in the treatment of cancer. In particular, described herein are methods for treating cancer comprising administering the chimeric Newcastle disease viruses in combination with an antagonist of PD-1 or a ligand thereof, wherein the chimeric Newcastle disease virus comprises a packaged genome comprising a transgene encoding interleukin-12.

The present invention provides methods for inducing regression of tumors in human subjects, the methods utilize a modified mesogenic strain of Newcastle disease virus (NDV) with modified F protein cleavage site, which is non-pathogenic to poultry (lentogenic), but exhibits oncolytic properties. The disclosed methods provide safe, effective and reliable means to induce regression of a tumor in an individual in need thereof. These methods overcome the drawbacks of using pathogenic strains of viruses for human therapy.