Abstract: The present disclosure relates to a sequential boost oncolytic viral immunotherapy and compositions for use in the same. More particularly, the disclosure relates to oncolytic viruses that significantly increase antigen-specific T cell-mediated immune responses when combined in a sequential heterologous boost treatment regimen.

Abstract: Various embodiments of the invention provide compositions of tumor infiltrating lymphocytes (TILs) enriched in tumor reactive cells. Embodiments also provide methods for manufacturing TILs enriched in tumor reactive cells and uses of the provided enriched tumor reactive TILs for treating cancer in a human or other subject. According to an embodiment, a pharmaceutical T lymphocyte infiltrating (TIL) composition enriched in tumor reactive T cells, comprises an oligoclonal population of tumor infiltrating T cells comprising CD4+ and CD8+ T cells from a tumor, wherein up to 40 clones make up at least 40% of the TCR frequency in the population. Embodiments of the invention are particularly useful for treating tumors that are or have become resistant or refractory to conventional chemotherapy.

Abstract: Various embodiments of the invention provide recombinant oncolytic viruses engineered to express human cytomegalovirus (HCMV) glycoprotein UL40 and/or Kaposi's sarcoma associated herpesvirus (KSHV) K5 protein, and methods and uses of the same for treating cancer. Also provided are combination therapies involving a T lymphocyte infiltrating (TIL) cell therapy and a provided recombinant oncolytic virus for treating a cancer, including solid tumors.

Abstract: Provided herein is a method for inducing an immune response to at least one neoantigen, the method comprising administering to a subject a priming composition comprising a peptide antigen conjugate and at least a first boost. The first boost comprises a first oncolytic virus comprising a genome that expresses a first peptide or a second peptide, wherein the first and second peptide are each capable of inducing an immune response to at least one neoantigen. The method further comprises administering the subject a second boost, comprising a second oncolytic virus comprising a genome that expresses a third peptide or a fourth peptide, wherein the third peptide and the fourth peptide are each capable of inducing an immune response to at least one neoantigen, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus. The subject may have pre-existing immunity to the at least one neoantigen.

Abstract: In one aspect, provided herein is a heterologous boost method for inducing an immune response to at least one neoantigen, the method comprising administering to a subject a first boost and subsequently administering to the subject a second boost, wherein the first boost comprises a first oncolytic virus comprising a genome that expresses, in the subject, a first peptide, or the first boost comprises a first oncolytic virus and a second peptide, wherein the second boost comprises a second oncolytic virus comprising a genome that expresses, in the subject, a third peptide, or the second boost comprises a second oncolytic virus and a fourth peptide, wherein the first peptide, the second peptide, the third peptide, and the fourth peptide are each capable of inducing an immune response to at least one neoantigen, and wherein the second oncolytic virus is immunologically distinct from the first oncolytic virus. The subject may have pre-existing immunity to the at least one neoantigen.

Abstract: The present disclosure relates to a sequential boost oncolytic viral immunotherapy and compositions for use in the same. More particularly, the disclosure relates to oncolytic viruses that significantly increase antigen-specific T cell-mediated immune responses when combined in a sequential heterologous boost treatment regimen.

Abstract: Described herein is an isolated viral particle having a genome that includes open reading frames that encode: Maraba proteins N, P, and L, or variants thereof; as well as Maraba protein M or protein delta 51M, or variants thereof; and a Bahia Grande G protein, a LCMV G protein, or an Ebola G protein. Maraba protein N may have a sequence which includes SEQ ID NO: 1. Maraba protein P may have a sequence which includes SEQ ID NO: 2. Maraba protein L may have a sequence which includes SEQ ID NO: 3. Maraba proteins M and delta 1M may have sequence which include SEQ ID NO: 4 and 5, respectively. Bahia Grande G protein may have a sequence which includes SEQ ID NO: 6. LCMV G protein may have a sequence which includes SEQ ID NO: 7. Ebola G protein may have a sequence which includes SEQ ID NO: 8.

Abstract: Embodiments of the invention include compositions and methods related to non-VSV rhabdoviruses and their use as anti-cancer therapeutics. Such rhabdoviruses possess tumor cell killing properties in vitro and in vivo.

Abstract: Embodiments of the invention include compositions and methods related to non-VSV rhabdoviruses and their use as anti-cancer therapeutics. Such rhabdoviruses possess tumor cell killing properties in vitro and in vivo.

Abstract: Disclosed are compositions and methods for augmenting activity of oncolytic viruses. Virus activity is augmented by sensitizing cancer or tumour cells through modulation of the Endoplasmic Reticulum (ER) stress response pathway, for instance by introducing into a tumour cell an agent effective to modulate ER stress response and sensitize the tumour cell. The tumour cells are then contacted with an oncolytic virus in an amount effective to reduce viability of the sensitized tumour cell. The oncolytic virus is thereby rendered more effective at lysing or killing the sensitized tumour or cancer cells.

Abstract: The present invention is directed to a method of reducing the viability of a tumor cell involving administering a virus that is not a common human pathogen to the tumor cell. Preferably, the virus exhibits differential susceptibility, in that normal cells are not affected by the virus. This differential susceptibility is more pronounced in the presence of interferon. The tumor cell is characterized by having low levels, or no, PKR activity, or as being PKR?/?, STAT1?/? or both PKR?/? and STAT1?/?. The virus is selected from the group consisting of Rhabdovirus and picomavirus, and preferably is vesicular stomatitis virus (VSV) or a derivative thereof.

Abstract: The subject invention relates to viruses that are able to purge (reduce or eliminate) undesirable cells in a mixture of cells. Undesirable cells can include neoplastic cells, cells mediating graft-versus host diseases, and autoimmune cells. The subject invention also relates to the purging of undesirable cells from bone marrow or peripheral blood cell harvests in the treatment of mammals including cancer patients, transplant recipients, and patients with autoimmune disease.