The invention refers to new immuno-modulated replication-efficient Vaccinia virus strain (IOVA) and its derivatives for the use in medicine.

The invention refers to new immuno-modulated replication-efficient Vaccinia virus strain (IOVA) and its derivatives for the use in medicine.

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 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.

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 aspects, the present disclosure provides a method of treating or preventing a uterine fibroid in a female mammal, the method comprising, consisting essentially of, or consisting of administering to the female mammal an effective amount of an agent that modulates an N6-methyladenosine (m6A) regulator.

In aspects, the present disclosure provides a method of treating or preventing a uterine fibroid in a female mammal, the method comprising, consisting essentially of, or consisting of administering to the female mammal an effective amount of an agent that modulates an N6-methyladenosine (m6A) regulator.

The invention provides methods of treating a cancer in a subject, comprising administering to the subject a combination of (a) an anti-neoplastic agent and (b) an agent that induces iron-dependent cellular disassembly, thereby treating the cancer in the subject. In some embodiments, the cancer is resistant to the anti-neoplastic agent.

The invention provides methods of treating a cancer in a subject, comprising administering to the subject a combination of (a) an anti-neoplastic agent and (b) an agent that induces iron-dependent cellular disassembly, thereby treating the cancer in the subject. In some embodiments, the cancer is resistant to the anti-neoplastic agent.