The disclosure provides Myxoma viruses that express one or more multi-specific immune cell engagers, such as BiKE, BiTE and/or MiTE and their use in inhibiting and/or treating a hematological cancer in a subject. The disclosure also provides a leukocyte having a Myxoma virus that expresses one or more multi-specific immune cell engagers, and the use of the leukocyte for inhibiting and/or treating a hematological cancer in a subject.

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 (MVA?E3L), 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 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 (MVA?E3L), 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.

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.

A replication-competent recombinant virus includes an expression cassette encoding a protein associated with arginine biosynthesis. The protein associated with arginine biosynthesis may include argininosuccinate synthase 1 (ASS1), argininosuccinate lyase (ASL), or ornithine transcarboxylase (OTC). The recombinant virus may be derived from a myxoma virus. A method of treating a cell includes contacting a cell with a recombinant virus including an expression cassette encoding a protein associated with arginine biosynthesis. The protein associated with arginine biosynthesis may be ASS1, ASL, OTC.

The present invention relates to therapeutic use of a combination of Myxoma virus, including in combination with rapamycin. Treatment with rapamycin enhances the ability of Myxoma virus to selectively infect cells that have a deficient innate anti-viral response, including cells that are not responsive to interferon. The combination of rapamycin and Myxoma virus can be used to treat diseases characterized by the presence of such cells, including cancer. The invention also relates to therapeutic use of Myxoma virus that does not express functional M135R.

The present invention relates to therapeutic use of a combination of Myxoma virus, including in combination with rapamycin. Treatment with rapamycin enhances the ability of Myxoma virus to selectively infect cells that have a deficient innate anti-viral response, including cells that are not responsive to interferon. The combination of rapamycin and Myxoma virus can be used to treat diseases characterized by the presence of such cells, including cancer. The invention also relates to therapeutic use of Myxoma virus that does not express functional M135R.

Myxoma viruses that are deficient in the activity of a Myxoma virus protein selected from the group consisting of M11L, M063, M 136, M-T4 and M-T7 are useful for treating cancer.

A composition for treating cancerous cells in a subject having an immune system includes a virus in the Yatapoxvirus genus having at least one mutation. In one embodiment, the mutation results in suppressed expression of a TNF binding protein by the virus. In another embodiment, the mutation results in suppressed expression of thymidine kinase (TK) by the virus. In another embodiment, the mutation arms the virus with a transgene to express a bacterial flagellin. The mutations can be present singly or in combination. Additional aspects include a method of treating cancerous cells with a composition as described herein, and a method of delivering at least one gene to cancerous cells in a subject.

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 (MVAE3L), 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.