Modified E1a regulatory sequences are provided, wherein at least one Pea3 binding site, or a functional portion thereof, is deleted. Also provided are modified E1a sequences that selectively express particular isoforms. Also provided is an E1b-19K clone insertion site. These modified sequences can be used individually, or in combination with one another, to provide tumor-selective expression of proteins.

Provided are methods and compositions for treating cancer with a combination of neural stem cells (NSCs) and an oncolytic virus or a combination of oncolytic virotherapy and immune modulation. The method entails administrating to a subject a pharmaceutical composition comprising a combination of NSCs and an oncolytic virus, and/or NSCs packaged with one or more immunomodulatory viruses expressing one or more immunity checkpoint inhibitors, including adaptive immunity checkpoint inhibitors and innate immunity checkpoint inhibitors. The immunity checkpoint inhibitors include shRNAs against the immunity checkpoint proteins. The cancer includes but is not limited to primary, recurrent, and metastatic brain cancer, breast cancer, head and neck cancer, bladder cancer, ovarian cancer, uterine cancer, prostate cancer, skin cancer, lung cancer, and colorectal cancer.

Mesenchymal stem cells for use as vehicles for therapeutic agents. The present invention is related to a method for selecting or obtaining mesenchymal stem cells (MSCs) that can be used as transporters or vehicles for therapeutic agents, especially in cancer treatment.

To increase the therapeutic potential of these oncolytic viruses based on a 24 base pair deletion in the viral E1 A gene (D24), a conditionally replicating adenovirus targeting multiple receptors upregulated on tumors was generated by incorporating an Ad5/3 fiber with a carboxyl terminus RGD ligand. The virus displayed full cytopathic effect in tumor lines assayed at low titers with improved cytotoxicity over Ad5-RGD D24, Ad5/3 D24 and an HSV oncolytic virus. The virus was further engineered to deliver immunotherapeutic agents such as GMCSF while maintaining enhanced heterogenic oncolysis.

The present disclosure provides a method of treating a human patient comprising the steps of: systemically administering multiple doses of a parenteral formulation of a replication capable oncolytic adenovirus of subgroup B in a single treatment cycle, wherein the total dose given in each dose is in the range of 1×10.sup.10 to 1×10.sup.14 viral particles, and wherein each dose of virus is administered over a period of 1 to 90 minutes, for example at a rate of viral particle delivery in the range of 2×10.sup.10 particles per minute to 2×10.sup.12 particles per minute. The disclosure further extends to formulations of the said oncolytic adenoviruses and combination therapies of the viruses and formulations with other therapeutic agents.

Disclosed is a nanoparticle comprising an inner core comprising a virus; and an outer surface comprising a cellular membrane derived from a cell, and process of making thereof. The virus is an oncolytic virus and cellular membrane is derived from for example red blood cells.

The invention relates to a recombinant adenovirus nucleic acid wherein the gene encoding protein V and/or the gene encoding protein VII is placed under control of a heterologous promoter, to a recombinant adenovirus nucleic acid wherein the adenoviral nucleotide sequence is mutated in such a way that it is no longer capable of producing one or more of the coat proteins, to cellular vesicles filled with such adenoviral material, cells provided with such adenoviral material and to methods and use thereof.

This disclosure describes oncolytic adenovirus constructs and methods on using the constructs. Generally, the oncolytic constructs includes at least a partial deletion of E3, a heterologous polynucleotide encoding a heterologous polypeptide in place of the at least partial deletion of E3, and a cell-specific regulatory polynucleotide operationally linked to the heterologous polynucleotide.

Disclosed herein are recombinant adenoviruses with one or more nucleotide sequences inserted between two viral transcription units, formulations comprising the recombinant adenoviruses, and methods of treatment using the recombinant adenoviruses. In some embodiments, the one or more nucleotide sequences are inserted in an IX-E2 insertion site and/or an L5-E4 insertion site.

Genetically modified rodents such as mice and rats, and methods and compositions for making and using the same, are provided. The rodents comprise a humanization of at least one endogenous rodent Tmprss gene, such as an endogenous rodent Tmprss2, Tmprss4, or Tmprss11d gene.