The invention relates to a recombinant Modified Vaccinia Virus Ankara (MVA) encoding a spike (S) protein or a part thereof, such as a receptor-binding domain (RBD), and additional antigenic sequences derived from other proteins of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19).

The invention relates, in general, to synthetic chimeric poxviruses, compositions comprising such viruses, and the development and use of systems and methods for producing such synthetic chimeric poxviruses. The synthetic chimeric poxviruses are well suited for live virus vaccines and pharmaceutical formulations.

The present disclosure provides a replication-competent, recombinant oncolytic vaccinia virus (OVV) comprising one of more of a) a nucleotide sequence encoding a variant A33 polypeptide, b) a nucleotide sequence encoding a variant A34 polypeptide, and c) a nucleotide sequence encoding a variant B5 polypeptide, wherein the variant A33, variant A34, and variant B5 polypeptides comprise one or more amino acid substitutions that provide for enhanced virus spreading or enhanced EEV production as compared with a virus encoding a corresponding wild-type A33, A 34, and B5 polypeptide. The present disclosure also provides compositions comprising the OVV and use of the OVV or the composition for inducing oncolysis in an individual having a tumor.

Clonal strains of vaccinia viruses are provided. Also provided are methods of identifying and isolating attenuated and oncolytic clonal strains from virus preparations. Modified recombinant forms of the clonal strains also are provided. The clonal strains and virus preparations can be used for diagnostic and therapeutic methods, in particular for therapy and diagnosis or monitoring treatment of proliferative disorders, including neoplastic diseases, such as, but are not limited to, solid tumors and blood cancers.

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 invention relates to a pharmaceutical composition for treating cancer comprising an anticancer virus, an immune checkpoint inhibitor and hydroxyurea as active ingredients. The pharmaceutical composition for treating cancer of the present invention, comprising an anticancer virus, an immune checkpoint inhibitor and hydroxyurea as active ingredients, has an excellent anticancer effect and safety as compared to a conventional case of single administration of an anticancer virus or combined administration of an anticancer virus and an immune checkpoint inhibitor. Accordingly, the pharmaceutical composition for treating cancer of the present invention, comprising an anticancer virus, an immune checkpoint inhibitor and hydroxyurea as active ingredients, may be effectively used in treating cancer.

A recombinant vaccinia virus containing a gene encoding sPD-1 or hyaluronidase and a pharmaceutical composition including the same are disclosed. The recombinant vaccinia virus containing a cancer therapy gene and having suppressed expression of K3L, TK, or VGF gene of the vaccinia virus has an excellent anti-tumor effect. Therefore, the recombinant vaccinia virus of the present invention can be advantageously used in cancer treatment.

Methods of infection, hold times and storage temperatures are provided to extend the viability and stabilize the phenotype of the cytolytic cells as a monotherapy and cytolytic cells containing an oncolytic virus capable of cell cycle arrest. Pre-infection of effector cells prior to storage at 4° C. or room temperature resulted in sustained viability of expanded immune cells and a higher percentage of CD3+/CD56+ T cells including a higher percentage of those CD3+/CD56+ T cells expressing the NKG2D receptor. In some embodiments, viral infection of immune cells increases the expression of the NKG2C, D and E receptors and influence the migration, binding and cytolytic activity towards tumor cells representing synergy between the immune cell and oncolytic virus in attacking and lysing tumor cells.

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.

The present invention relates to oncolytic vaccinia viruses which have been modified to promote anti-tumor immunity and/or reduce host immunity and/or antibody response against the virus. It is based, at least in part, on the discovery that oncolytic vaccinia virus (i) bearing a genome deletion of a gene that reduces T cell immunity (interleukin-18 binding protein); (ii) treated with a sialidase enzyme which is believed to reduce TLR2 activation and therefore the antibody response; (iii) carrying a gene that enhances cytotoxic T lymphocyte induction (e.g., TRIF) and/or (iv) reduces tumor myeloid-derived suppressor cells by reducing prostaglandin E2 reduces tumor growth. Accordingly, the present invention provides for immunooncolytic vaccinia viruses and methods of using them in the treatment of cancers.