The disclosure provides Myxoma vims that expresses one or more immunomodulatory transgenes and its use in inhibit-mg and/or treating a hematological cancer in a subject. The disclosure also provides a leukocyte having a Myxoma virus that expresses one or more immunomodulatory transgenes and the use of the leukocyte for inhibiting and/or treating a hematological cancer in a subject.

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

Provided is a composition and method for treating cancer in a patient in need of cancer treatment, and the cancer can be treated by a combined therapeutic use of squirrel poxvirus and myxoma poxvirus.

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.

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 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 Fins-like 5 tyrosine kinase 3 ligand (hFlt3L) isolated, suitable for use as an immunotherapeutic agent against a malignant solid tumor.

An oncolytic poxvirus encoding a truncated human CD19 is used in conjunction with a chimeric antigen receptor to treat solid tumors.

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 disclosure provides Myxoma virus that expresses one or more immunomodulatory transgenes and its 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 immunomodulatory transgenes and the use of the leukocyte for inhibiting and/or treating a hematological cancer in a subject.

Disclosed herein, in certain embodiments, are recombinant myxoma viruses (MYXVs) and nucleic acid constructs encoding the recombinant oncolytic virus genomes and parts thereof. In some embodiments, the nucleic acid constructs include at least a portion of myxoma virus (MYXV) genome and a transgene (e.g., IL-12) driven by poxvirus P11 late promoter. The transgene is inserted at the MYXV genome to reduce or disrupt the expression of M153 gene of the MYXV genome.