The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises: (i) a mitogenic T-cell activating transmembrane protein which comprises a mitogenic domain and a transmembrane domain; and/or (ii) a cytokine-based T-cell activating transmembrane protein which comprises a cytokine domain and a transmembrane domain, wherein the mitogenic or cytokine-based T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells of Natural Killer cells are transduced by such a viral vector, they are simultaneously activated by the mitogenic T-cell activating transmembrane protein and/or the cytokine-based T-cell activating transmembrane protein.

In one embodiment, the invention provides an HSV vector comprising a mutant gB and/or a mutant gH glycoprotein, where the viral envelope further comprises a non-native ligand specific for a protein present on the surface of a predetermined cell type. In another embodiment, the invention provides an HSV vector comprising (a) a mutant gC and/or gD envelope glycoprotein which comprises a non-native ligand specific for a protein present on the surface of a predetermined cell type; and (b) a mutant envelope glycoprotein other than gD.

The present invention provides a composition comprising i) a pseudotyped retroviral vector particle comprising a) one envelope protein with antigen-binding activity, wherein said envelope protein is a recombinant protein that does not interact with at least one of its original receptors and is fused at its ectodomain to a polypeptide comprising an antigen binding domain specific for CD62L, and wherein said envelope protein is protein G, HN or H derived from the Paramyxoviridae family, b) one envelope protein with fusion activity derived from the Paramyxoviridae family, and T cells expressing CD62L. Alternatively, when said polypeptide comprising an antigen binding domain is specific for a tag of a tagged polypeptide instead of the antigen binding domain specific for CD62L, wherein said tagged polypeptide binds specifically to CD62L, then the composition comprises further said tagged polypeptide.

Oncolytic viruses offer an in situ vaccination approach to activate tumor-specific T cell responses. However, the upregulation of PD-L1 expression on tumor cells and immune cells leads to tumor resistance to oncolytic immunotherapy. Herein, we generate an engineered oncolytic virus that coexpresses a PD-L1 inhibitor and GM-CSF. This oncolytic virus is capable of secreting the PD-L1 inhibitor that systemically binds and inhibits PD-L1 on tumor cells and immune cells. The intratumoral injection with the oncolytic virus overcomes PD-L1-mediated immunosuppression during both the priming and effector phases, provokes systemic T cell responses against dominant and subdominant neoantigen epitopes derived from mutations, and leads to an effective rejection of both virus-injected and distant tumors. This engineered oncolytic virus allows for activation of tumor neoantigen-specific T cell responses, providing a potent, individual tumor-specific oncolytic immunotherapy for cancer patients, especially those resistant to PD-1/PD-L1 blockade therapy.

The present invention provides a kit of vectors comprising: (i) a first vector comprising a nucleic acid sequence encoding a first marker component; and (ii) a second vector comprising a nucleic acid sequence encoding a second marker component, wherein, when a cell is transduced with both the first and second vectors, the first and second marker components are expressed by the cell and associate forming a hetero-multimeric marker which is recognised by a cell sorting reagent whereas, when a cell is transduced with either the first or second vector alone, expression of the first or second marker component alone is not recognised by the cell sorting reagent.

The present invention provides a composition comprising i) a pseudotyped retroviral vector particle or virus-like particle thereof comprising a) one envelope protein with antigen-binding activity, wherein said envelope protein is a recombinant protein that does not interact with at least one of its native receptor(s) and is fused at its ectodomain to a polypeptide comprising an antigen binding domain specific for a tag of a tagged polypeptide, and wherein said envelope protein is protein G, HN or H derived from the Paramyxoviridae family, and b) one envelope protein with fusion activity derived from the Paramyxoviridae family, and ii) said tagged polypeptide, wherein said tagged polypeptide binds specifically to an antigen expressed on the surface of a target cell, thereby transducing the target cell with said retroviral vector particle or thereby inducing uptake of the virus-like particle into the target cell. A pharmaceutical composition thereof and an in vitro method for transduction of targets cells with said vector particle are also disclosed.

The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises: (i) a mitogenic T-cell activating transmembrane protein which comprises a mitogenic domain and a transmembrane domain; and/or (ii) a cytokine-based T-cell activating transmembrane protein which comprises a cytokine domain and a transmembrane domain, wherein the mitogenic or cytokine-based T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells of Natural Killer cells are transduced by such a viral vector, they are simultaneously activated by the mitogenic T-cell activating transmembrane protein and/or the cytokine-based T-cell activating transmembrane protein.

This document provides methods and materials related to vesicular stomatitis viruses. For example, replication-competent vesicular stomatitis viruses, nucleic acid molecules encoding replication-competent vesicular stomatitis viruses, methods for making replication-competent vesicular stomatitis viruses, and methods for using replication-competent vesicular stomatitis viruses to treat cancer or infectious diseases are provided.

The present invention relates to a viral complex comprising a viral vector capable of delivering shRNA that suppresses an expression of epidermal growth factor receptor (EGFR) to a cell and an anti-epithelial cell adhesion molecule (EpCAM) antibody conjugated to the viral vector, a pharmaceutical composition for preventing or treating cancer, comprising the viral complex, and a method for treating cancer, comprising administering the viral complex or the pharmaceutical composition to a subject in which a cancer disease has occurred and overexpressing EpCAM. The anti-EpCAM antibody-AAV2/shEGFR complex provided in the present invention significantly reduces the expression level of EGFR in tumor cells overexpressing EpCAM without inducing an immune response in vivo, thereby inducing death of tumor cells, and thus, it can be widely utilized in more effective and safe cancer treatment.

Disclosed herein are compositions of retroviruses and methods of using the same for gene delivery, wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.