The present invention discloses a modified interleukin 12 (nsIL-12) and its gene, recombinant vector and use in manufacture of a medicament for treatment of tumors. When the oncolytic adenovirus vector carrying the modified interleukin 12 gene targets tumor tissue, the modified interleukin 12 is continuously expressed at a low level and mainly distributed in the local tumor tissue, which improves the specificity to tumor cells and reduces the systemic toxicity of interleukin 12; the modified interleukin 12 shows stronger inhibitory effect on tumor growth in intraperitoneally disseminated tumors and orthotopic tumors, and has low toxicity. The modified interleukin 12 armed oncolytic viruses show excellent anti-tumor effects, with a significant regression of tumors and lower toxicity compared with the existing IL-12 armed virus.

The present invention discloses a modified interleukin 12 (nsIL-12) and its gene, recombinant vector and use in manufacture of a medicament for treatment of tumors. When the oncolytic adenovirus vector carrying the modified interleukin 12 gene targets tumor tissue, the modified interleukin 12 is continuously expressed at a low level and mainly distributed in the local tumor tissue, which improves the specificity to tumor cells and reduces the systemic toxicity of interleukin 12; the modified interleukin 12 shows stronger inhibitory effect on tumor growth in intraperitoneally disseminated tumors and orthotopic tumors, and has low toxicity. The modified interleukin 12 armed oncolytic viruses show excellent anti-tumor effects, with a significant regression of tumors and lower toxicity compared with the existing IL-12 armed virus.

The present invention provides a genetically recombinant vaccinia virus effective in preventing or treating cancer. Specifically, the present invention provides a recombinant vaccinia virus lacking functions of VGF and O1L and having a gene encoding B5R in which an SCR domain has been deleted. Specifically, the present invention provides a vaccinia virus comprising two polynucleotides, a polynucleotide encoding IL-7 and a polynucleotide encoding IL-12; a combination kit of two vaccinia viruses, a vaccinia virus comprising a polynucleotide encoding IL-7 and a vaccinia virus comprising a polynucleotide encoding IL-12; and use of the two vaccinia viruses in combination.

An engineered vaccinia virus, a pharmaceutical composition containing the same, and methods for use in treating a subject in need using the same are provided. The engineered vaccinia virus includes a mutated viral sequence and a heterologous sequence. The mutated viral sequence is used for selective replication in tumor cells and/or activation of immune cells. The heterologous sequence encodes an immune co-stimulatory pathway activating molecule, immunomodulator gene, a truncated viral envelope gene, and/or a tumor suppressor. The heterologous sequence is stably incorporated into the genome of the engineered vaccinia virus. The pharmaceutical composition includes an effective amount of the engineered vaccinia virus and a pharmaceutical acceptable vehicle. The methods for use in treating the subject in need include administering the engineered vaccinia virus to the subject.

The compositions and methods are described for generating an immune response to a hemorrhagic fever virus such as ebolavirus, Marburgvirus, or arenavirus. The compositions and methods described herein relate to a modified vaccinia Ankara (MVA) vector encoding one or more viral antigens for generating a protective immune response to a member of genus Ebolavirus (such as a member of species Zaire ebolavirus), a member of genus Marburgvirus (such as a member of species Marburg marburgvirus), or a member of genus Arenavirus (such as a member of species Lassa virus) in the subject to which the vector is administered. The compositions and methods of the present invention are useful both prophylactically and therapeutically and may be used to prevent and/or treat an infection caused by ebolavirus, Marburgvirus, or arenavirus.

The compositions and methods are described for generating an immune response to a hemorrhagic fever virus such as ebolavirus, Marburgvirus, or arenavirus. The compositions and methods described herein relate to a modified vaccinia Ankara (MVA) vector encoding one or more viral antigens for generating a protective immune response to a member of genus Ebolavirus (such as a member of species Zaire ebolavirus), a member of genus Marburgvirus (such as a member of species Marburg marburgvirus), or a member of genus Arenavirus (such as a member of species Lassa virus) in the subject to which the vector is administered. The compositions and methods of the present invention are useful both prophylactically and therapeutically and may be used to prevent and/or treat an infection caused by ebolavirus, Marburgvirus, or arenavirus.

The invention relates to vectors comprising two or more homologous nucleotide sequences and methods for generating them. The invention concerns substituting bases in the homologous nucleotide sequences with different bases that do not alter the encoded amino acid sequence. The invention allows for the reduction of intramolecular recombination between homologous nucleotide sequences, in particular in mammalian cells. The invention further relates to nucleotide sequences containing substituted bases.

Provided herein are recombinant poxviruses that are stable through successive passaging of the recombinant poxviruses. More particularly, the recombinant poxviruses comprise one or more modified nucleic acids encoding MUC1, CEA, and/or TRICOM antigens, wherein the recombinant poxviruses are stable through successive passaging. Also, provided herein are compositions and method related thereto.

Provided herein are recombinant poxviruses that are stable through successive passaging of the recombinant poxviruses. More particularly, the recombinant poxviruses comprise one or more modified nucleic acids encoding MUC1, CEA, and/or TRICOM antigens, wherein the recombinant poxviruses are stable through successive passaging. Also, provided herein are compositions and method related thereto.

The present invention provides an oncolytic virus comprising nucleotide sequence(s) encoding one or more immune checkpoint modulator(s). It also concerns a pharmaceutical composition comprising effective amount of said oncolytic virus and, eventually, a pharmaceutically acceptable vehicle and its use for treating proliferative diseases such as cancers.