There is described herein a non-replicating Rhabdovirus-derived particle that lacks the ability to spread between cells while having tropism against immortalized cells. The non-replicating Rhabdovirus-derived particle may have cytolytic tropism against immortalized cells. There is also described a non-replicating Rhabdovirus-derived particle that lacks the ability to spread between cells but has innate and/or adaptive immune-stimulating properties.

This disclosure relates to novel triple combination therapies of an oncolytic virus, a PD-1 pathway inhibitor, and a CTLA4 inhibitor for treating or inhibiting the growth of a tumor in a patient with cancer.

The present invention relates to: a virus-containing pharmaceutical composition, which comprises, as an active ingredient, a virus for treating or preventing disease; and a preparation method therefor.

Provided are a pharmaceutical composition for treatment of a tumor or cancer, and an application thereof. The pharmaceutical composition comprises an oncolytic rhabdovirus and a small molecule CD38 inhibitor such as rhein that are administered via direct local injection or systemic administration or intratumoral delivery. The oncolytic rhabdovirus has the characteristic of recognizing tumor cells and would not cause damage to normal cells. Meanwhile, the small molecule CD38 inhibitor has the activity of specifically inhibiting T-cell receptor molecules. The combined use of the oncolytic rhabdovirus and the small molecule CD38 inhibitor has significant advantages in safety and efficacy.

The disclosure provides methods and materials for treating cancer. Specifically, the disclosure provides a chimeric vesiculovirus comprising: (a) a first genomic fragment of a first vesiculovirus species; and (b) a second genomic fragment of a second vesiculovirus species different from said first vesiculovirus species; wherein the vesiculovirus species comprising vesicular stomatitis viruses (VSVs) and morreton Virus (MorV). Further disclosed are methods of using chimeric vesiculoviruses as oncolytic agents for treating cancer.

The present invention pertains to the provision of a vaccine comprising a first component (K) and a second component (V), wherein the first component (K) comprises a complex in which a cell penetrating peptide, an antigenic domain and a TLR agonist are functionally linked and the second component (V) comprises an oncolytic recombinant vesicular stomatitis virus expressing an antigenic domain. The invention further pertains to the use of the inventive vaccine in the treatment of cancer. The invention also provides a recombinant vesicular stomatitis virus expressing an antigenic domain and its use in cancer vaccines.

Chimeric viruses having a vesicular stomatitis virus (VSV) background where the VSV G protein is supplemented or replaced with an alphavirus glycoprotein(s), or a functional fragment(s) thereof, are provided. A preferred alphavirus is Chikungunya virus. In particular embodiments, the glycoprotein(s) is or includes E3, E2, K6, and E1 proteins of an alphavirus, preferably Chikungunya virus. Methods of using the chimeric viruses for treatment of cancers, particularly brain cancers and metastasis thereof are also provided. In some embodiments, the chimeric viruses retain superior oncolytic activity to infect and destroy cancer cells selectively, such as glioblastoma and intracranial melanoma metastases. In some embodiments, the chimeric viruses have reduced toxicity to e.g., heathy cells relative to a control such as the parent VSV with the VSV G protein.

The present invention relates to recombinant oncolytic viruses comprising a vesicular stomatitis virus (VSV), wherein the glycoprotein (G protein) of VSV is deleted; and which comprises a modified fusion protein (F protein) of Newcastle disease virus (NDV); and the hemagglutinin neuraminidase (HN) protein of NDV. The present invention further relates to nucleic acids encoding for the recombinant oncolytic virus and vectors comprising the nucleic acids. The present invention further relates to pharmaceutical compositions comprising the rVSV of the invention, the nucleic acid or the vector, further to uses as gene delivery tool and/or for tumor detection. The present invention further relates to the recombinant oncolytic vesicular stomatitis virus (VSV) for use in medicine, in particular for the diagnosis, prevention and/or treatment of cancer.

Described herein are pseudotyped oncolytic viruses comprising nucleic acids encoding an engager molecule. In some embodiments, the pseudotyped oncolytic viruses comprises nucleic acids encoding an engager molecule and one or more therapeutic molecules. Pharmaceutical compositions containing the pseudotyped oncolytic virus and methods of treating cancer using the pseudotyped oncolytic viruses are further provided herein.

The present invention provides an oncolytic virus vector containing a sequence encoding IL-4 receptor targeted cargo protein, including IL-4 muteins and/or IL-13 muteins, the oncolytic virus encoded therefrom, the uses of the oncolytic virus for treating cancer.