Provided are immunostimulatory bacteria and oncolytic viruses, and pharmaceutical compositions containing the bacteria and/or viruses, that act as three prime repair exonuclease 1 (TREX1) antagonists. The bacteria and viruses are for treating tumors that are human papillomavirus (HPV) positive or that have a high tumor mutational burden (TMB). The immunostimulatory bacteria and oncolytic viruses encode therapeutic products such RNAi, such as shRNA and microRNA, that mediate gene disruption and/or inhibit expression of TREX1, or that inhibit TREX1. The bacteria contain additional modifications to enhance their anti-tumor activity. The bacteria and viruses are used for treatment of tumors in which TREX1 expression correlates with the presence of the tumor or properties of the tumor, such that inhibition of TREX1 advantageously treats the tumor.

The technology of the present disclosure relates to the use of Heat-inactivated modified vaccinia Ankara (MVA) vims (Heat-iMVA) or Heat-inactivated vaccinia vims as a vaccine immune adjuvant. In particular, the present technology relates to the use of Heat-iMVA as a vaccine adjuvant for tumor antigens in cancer vaccines alone or in combination with immune checkpoint blockade (ICB) antibodies for use as a cancer immunotherapeutic.

Compositions and methods are provided for treating cancer comprising a composition comprising an oncolytic virus and a targeting moiety on the surface of the virus, wherein the oncolytic virus does not encode or express the targeting moiety within various aspects such compositions and methods can be used to treat a wide variety of cancers (e.g., gastrointestinal cancer, such as esophageal, stomach and colon cancers).

The present disclosure provides compositions and methods related to the modulation of the inflammation response activated by a host's immune system. In particular, the present disclosure provides novel inhibitors of proteins that exhibit pro-inflammatory activity (e.g., RIPK1, RIPK3, ZBP1, TRIF, CUL1, SKP1, and NF-B, among others), as well as corresponding therapeutic compositions and methods of treatment using these inhibitors.

An object of the present invention is to provide a protective method for liver comprising the administration of an extract from inflamed tissues inoculated with vaccinia virus to a patient who needs the treatment and to provide a liver protective agent, etc. where such an extract is an active ingredient. In the present invention, it has been recognized that, in hepatocytes, activation of NF-B, expression of NF-B target genes, activation of JNK, apoptosis and fat accumulation can be inhibited or suppressed. The agent containing the extract as an active ingredient is a drug exhibiting less adverse action and high safety. Accordingly, the present invention provides very useful protective method for liver and liver protecting agent.

The present invention relates generally to the fields of oncology, virology and immunotherapy. More particularly, it concerns the use of poxviruses, specifically the replication competent attenuated vaccinia virus with deletion of thymidine kinase (VC-TK.sup.) with and without the expression of human Flt3L or GM-CSF as oncolytic and immunotherapy. The foregoing poxviruses can also be used in combination with immune checkpoint blocking agents. The foregoing poxviruses can also be inactivated via Heat or UV-treatment and the inactivated virus can be used as immunotherapy either alone or in combination with immune checkpoint blocking agents.

Provided herein are enhanced systems for potentiating cell-mediated oncolytic viral therapy. Also provided are modified viruses for such systems, and methods of treatment of cancers by administering such systems.

Provided are immunostimulatory bacteria and oncolytic viruses, and pharmaceutical compositions containing the bacteria and/or viruses, that act as three prime repair exonuclease 1 (TREX1) antagonists. The bacteria and viruses are for treating tumors that are human papillomavirus (HPV) positive or that have a high tumor mutational burden (TMB). The immunostimulatory bacteria and oncolytic viruses encode therapeutic products such RNAi, such as shRNA and microRNA, that mediate gene disruption and/or inhibit expression of TREX1, or that inhibit TREX1. The bacteria contain additional modifications to enhance their anti-tumor activity. The bacteria and viruses are used for treatment of tumors in which TREX1 expression correlates with the presence of the tumor or properties of the tumor, such that inhibition of TREX1 advantageously treats the tumor.

Disclosed are means, methods, and compositions of matter useful for generation of viruses that selectively grow in the tumor endothelium and causes lysis or augmentation of tumor immunity. In one embodiment an oncolytic virus is selectively maintained in cells resembling tumor endothelium under conditions allowing for the oncolytic virus to capture immunogenic entities found on the cells resembling tumor endothelial cells. In another embodiment, the endothelial cells resembling tumor endothelial cells are utilized as a Trojan horse for selective delivery of virus into a tumor or tumor microenvironment.

The present invention relates generally to the fields of oncology, virology and immunotherapy. More particularly, it concerns the use of poxviruses, specifically the replication competent attenuated vaccinia virus with deletion of thymidine kinase (VC-TK.sup.?) with and without the expression of human Flt3L or GM-CSF as oncolytic and immunotherapy. The foregoing poxviruses can also be used in combination with immune checkpoint blocking agents. The foregoing poxviruses can also be inactivated via Heat or UV-treatment and the inactivated virus can be used as immunotherapy either alone or in combination with immune checkpoint blocking agents.