A recombinant myxoma virus that encodes the orfC gene of walleye dermal sarcoma virus (WDSV). The orfC gene of walleye dermal sarcoma virus (WDSV) plays a role in induction of seasonal regression of tumors caused by WDSV. This gene was isolated from WDSV and recombined into myxoma virus (MYXV orfC) for use as an oncolytic therapy. The recombinant myxoma virus can be used in oncolytic virus therapy to specifically target and lyse cancer cells without harming healthy cells in cancer patients.

Disclosed herein, in certain embodiments, are recombinant myxoma viruses (MYXVs) and nucleic acid constructs encoding the recombinant MYXVs. In some embodiments, the MYXVs are engineered to inactivate or attenuate an activity or expression level of an M153 protein. In some embodiments, the MYXVs are engineered to express one or more transgenes such as a tumor necrosis factor (TNF), interleukin-12 (IL-12), or decorin. Also disclosed herein, in certain embodiments, are methods of using the MYXVs. Some embodiments include providing a MYXV as described herein to a subject in need thereof.

The present disclosure relates generally to the fields of oncology, virology and immunotherapy. It concerns poxviruses, specifically the highly attenuated modified vaccinia virus Ankara (MVA), and a recombinant modified vaccinia Ankara virus with deletion of vaccinia virulence factor E3 (MVAΔE3L), each further modified to express human Fms-like tyrosine kinase 3 ligand (Flt3L) or GM-CSF. The disclosure relates to use of the foregoing recombinant viruses as cancer immunotherapeutic agents. The foregoing recombinant poxviruses can also be used in combination with immune checkpoint blockade therapy.

The present disclosure provides a recombinant oncolytic myxoma vims engineered to express a soluble form of an immune checkpoint protein in conjunction with a cytokine/chemokine and/or a tumor antigen. In certain aspects, the oncolytic myxoma virus is a replication competent virus such as myxoma vims. Methods of cancer treatment comprising administering the recombinant oncolytic myxoma virus expressing the soluble form of the immune checkpoint protein are also provided.

Therapeutic methods for administering gut microbiota and oncolytic viruses to a subject are provided. The gut microbiota serve to pre-condition, the subject's immune system to antitumor responses and augments anticancer activity of the oncolytic vims. Combinations of the gut, microbiota and viruses and uses thereof for treating and preventing cancer are provided. The present disclosure also provides methods for building elite responder selection platforms through hierarchical clustering analysis of genomic profiles for human gut microbiome.

Therapeutic methods for administering gut microbiota and oncolytic viruses to a subject are provided. The gut microbiota serve to pre-condition, the subject's immune system to antitumor responses and augments anticancer activity of the oncolytic vims. Combinations of the gut. microbiota and viruses and uses thereof for treating and preventing cancer are provided. The present disclosure also provides methods for building elite responder selection platforms through hierarchical clustering analysis of genomic profiles for human gut microbiome.

Disclosed herein are methods and compositions of treating cancer, comprising administrating to a subject with cancer a therapeutically effective amount of an oncolytic virus and a nucleocytoplasmic transport inhibitor. Further described herein are methods of converting a nonpermissive cancer cell to a permissive cancer cell and methods of killing a cancer cell by contacting the cancer cell with a therapeutically effective amount of an oncolytic vims and a nucleocytoplasmic transport inhibitor.

The present invention relates generally to the fields of oncology, virology and immunotherapy. More particularly, it concerns the use of a recombinant modified vaccinia Ankara (MVA) virus comprising an MVA harboring a human Fms-like tyrosine kinase 3 ligand (hFlt3L) (MVA-hFtl3L). The foregoing vaccinia Ankara (MVA) virus can be delivered to tumor cells of a subject afflicted with a malignant solid tumor, to treat the tumor. In a related aspect, the present disclosure concerns a recombinant modified vaccinia Ankara virus with deletion of vaccinia virulence factor E3 (MV At.E3L) modified to express human Fms-like 5 tyrosine kinase 3 ligand (hFlt3L) isolated, suitable for use as an immunotherapeutic agent against a malignant solid tumor.

Provided herein are methods for inhibiting and/or treating a hematological cancer in a subject in need thereof using a myxoma virus that expresses one or more immunomodulatory transgenes, which includes FAST p14.

Disclosed herein, in certain embodiments, are recombinant myxoma viruses (MYXVs) and nucleic acid constructs encoding the recombinant MYXVs. In some embodiments, the MYXVs are engineered to inactivate or attenuate an activity or expression level of an M153 protein. In some embodiments, the MYXVs are engineered to express one or more transgenes such as a tumor necrosis factor (TNF), interleukin-12 (IL-12), or decorin. Also disclosed herein, in certain embodiments, are methods of using the MYXVs. Some embodiments include providing a MYXV as described herein to a subject in need thereof.