An engineered Newcastle Disease Virus (NDV) vector is provided. In particular, the present disclosure provides methods of treating or preventing a disease such as cancer, or an infectious disease, or methods for eliciting an immune response, with the engineered NDV vector. The engineered NDV vector provided herein is useful as an immunogenic composition, an oncolytic agent, or a vaccine.

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.

The invention relates to a novel Newcastle Disease Viruses (NDV) and transgene expressing Newcastle Disease Viruses (NDV), which have been demonstrated to possess significant oncolytic activity against mammalian cancers and an improved safety profile. The invention provides novel oncolytic viruses through the use of genetic engineering, including the transfer of foreign genes or parts thereof. The present invention also provides nucleic acids encoding a reverse genetically engineered (rg-)NDV comprising one or more of these foreign genes and 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, as well as a mutation in the F gene, said mutation resulting in a reduced ICPI value as compared to an otherwise identical rgNDV not having said at least one mutation in the F gene.

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.

The invention relates to transgene expressing Newcastle Disease Viruses (NDV), which have been demonstrated to possess significant oncolytic activity against mammalian cancers and/or an improved safety profile. The invention provides novel oncolytic viruses through the use of genetic engineering, including the transfer of foreign genes or parts thereof, such as genes encoding Atezolizumab or Bevacizumab. The present invention also provides nucleic acids encoding a reverse genetically engineered (rg-)NDV comprising one or more of these foreign genes and 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.

The present disclosure relates to an M2-LVP-K1 virus including a colorectal cancer cell-specific mutant sialic acid binding domain and a composition for treating colorectal cancer including the same. The mutant sialic acid binding domain of the present disclosure is constructed using directed evolution technology, and is a recombinant Newcastle disease virus constructed by substituting a normal sialic acid binding domain for a HN protein, a cell-binding receptor, to improve the specific infectivity to HCT116 cells. It was identified that M2-LVP-K1 recombinant Newcastle disease virus with improved colorectal cancer cell-specific infectivity has improved HCT116 cell death effect compared to the conventional normal recombinant Newcastle disease virus, and produces an excellent effect in inhibiting cancer tissue growth through in vivo experiments. The mutant recombinant Newcastle disease virus presented in this study relates to a therapeutic viral agent capable of inducing clinical symptom reduction, partial remission, or complete remission through colorectal cancer cell death or colorectal cancer tissue shrinkage.

In one aspect, provided herein are methods for treating cancer in a subject, comprising administering to a subject an oncolytic virus (e.g., an avian paramyxovirus (AMPV)) and a vascular endothelial growth factor (VEGF)-C agent, a VEGF-D agent, or a VEGF receptor (VEGFR)-3-activating agent. In another aspect, provided herein are oncolytic viruses (e.g. APMV) comprising a genome, wherein the genome comprises a transgene that comprises a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent or a VEGF receptor (VEGFR)-3-activating agent. In another aspect, provided herein are methods for treating cancer, comprising administering to a subject an oncolytic virus (e.g. APMV), wherein the oncolytic virus comprises a genome that comprises a transgene comprising a nucleotide sequence encoding a VEGF-C agent, a VEGF-D agent, or a VEGF receptor (VEGFR)-3-activating agent.

The invention relates to a pharmaceutical formulation comprising at least three recombinant transgene expressing Newcastle Disease Virus (NDV) strains, which have been demonstrated to possess significant oncolytic activity against mammalian cancers and an improved safety profile, a non-recombinant NDV strain, a reovirus type-3 and optionally a vaccinia virus. At least one of the recombinant NDV strains comprises in its viral genome a nucleic acid sequence comprising at least one foreign gene, the at least one foreign gene encoding a checkpoint modulator, and at least one of the recombinant NDV strains comprises in its viral genome a nucleic acid sequence comprising at least one foreign gene, the at least one foreign gene encoding an angiogenesis inhibitor. The viral genome of each of the at least three recombinant NDV strains comprises 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 NDV not having said mutation in the HN gene. The pharmaceutical formulation provides an improved treatment of cancer, because instead of a monotherapy, a mixture of oncolytic viruses is applied.

A recombinant Newcastle disease virus and a preparation method therefor, a recombinant plasmid, and use thereof. The recombinant Newcastle disease virus is obtained by replacing an F protein of a Newcastle disease virus lasota with an F protein of a Newcastle disease virus virulent strain. The recombinant chimeric virus has good safety and is capable of effectively inhibiting tumour cells, promoting tumour cell apoptosis, and effectively treating a tumour.

The invention relates to transgene expressing Newcastle Disease Viruses (NDV), which have been demonstrated to possess significant oncolytic activity against mammalian cancers. The invention provides novel oncolytic viruses through the use of genetic engineering, including the transfer of foreign genes or parts thereof, such as genes encoding Ipilimumab, interleukin-12 or NS1. The present invention also provides nucleic acids encoding a reverse genetically engineered (rg-)NDV comprising one or more of these foreign genes and 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.