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.

An immunogenic composition for reducing the incidence or severity of subclinical and clinical signs of orthoreovirus infection is provided. The composition(s) includes at least one segment or portion thereof of orthoreovirus that is derived from a different serotype, host, or strain than at least one other segment or portion thereof. The present disclosure also provides methods for treating, preventing, and reducing the subclinical and clinical signs of orthoreovirus infection in a subject or group of subjects.

Provided herein are methods of treating cancer in a subject. The methods include administering to the subject one or more doses of an oncolytic virus (e.g., in an initial round of treatment); selecting a subject with a T-cell population exhibiting high peripheral clonality; and administering to the subject with a T-cell population exhibiting high peripheral clonality a one or more subsequent doses of the oncolytic virus (e.g., in a second round of treatment).

The present disclosure relates to one or more modified avian-virus based agents, therapies, treatments, and methods of use of the modified avian-virus based agents and/or therapies and/or treatments for cancer. The disclosure also provides for methods of generating modified avian-virus based agents.

The present disclosure relates to one or more modified avian-virus based agents, therapies, treatments, and methods of use of the modified avian-virus based agents and/or therapies and/or treatments for cancer. The disclosure also provides for methods of generating modified avian-virus based agents.

Compositions and methods are provided that relate to an attenuated reovirus exhibiting oncolytic activity toward cancer cells while displaying reduced lytic activity toward non-malignant cells. Exemplified is an attenuated human reovirus derived from persistently infected fibrosarcoma cells that lacks wild-type reovirus S1 and S4 genes and consequently lacks a detectable reoviral outer capsid .sigma.1 protein and expresses a mutated reoviral outer capsid .sigma.3 protein.

Disclosed are recombinant oncolytic viruses that express one or more reovirus fusion-associated small transmembrane FAST) proteins and uses thereof. The oncolytic activity of the recombinant oncolytic viruses expressing FAST proteins can be used to treat primary and metastatic cancers, especially from breast and colon cancers.

The present invention provides an oncolytic virus formulation and preparation method thereof. The oncolytic virus formulation comprises cell vesicles derived from apoptotic tumor cells and oncolytic viruses coated in the cell vesicles as an effective component. The oncolytic virus formulation uses cell vesicles derived from tumor cells themselves to coat the oncolytic viruses, so as to evade the body's immune system attack and can be targeted to the tumor treatment site, and improve the tumor-killing effect.

Provided is a modified reovirus, a pharmaceutical composition thereof, and a method of treating cancer using the same which not only has an excellent anticancer effect on various cancers, including rare cancers, but can also enhance the effect of cancer immunotherapy agents.

Disclosed are means of treatment of cancer by enhancing efficacy of oncolytic virus ability to eradicate tumors through the destruction/inactivation of cancer endothelial cells through immunological means. In one embodiment of the invention, administration of placental endothelial cells generated antitumor endothelial immune responses are used to sensitize tumors to oncolytic viral entry. In another embodiment, oncolytic viruses are utilized to enhance generation of cancer endothelial specific responses by causing localized inflammation in the tumor endothelium, which enhances efficacy of the tumor endothelial targeting vaccine. In another embodiment, the invention teaches the use of replication deficient oncolytic viruses to deliver proteins to tumor cells in an immunogenic manner such that proteins encoded by the oncolytic viruses induce immunity to tumor endothelial cell antigens.