35 results about "Oncolytic virus" patented technology

The application discloses a recombinant oncolytic virus targeting CD317 gene and application thereof in anti-tumor, and belongs to the technical field of tumor treatment. The recombinant oncolytic virus comprises a CD317 inhibitor and an oncolytic virus, and is formed by integrating the CD317 inhibitor into the oncolytic virus genome. The CD317 inhibitor is a substance capable of inhibiting CD317 gene expression or targeting degradation of CD317 protein function, and is selected from shRNA or siRNA targeting CD317. The application develops the oncolytic virus targeting knockdown of CD317 expression, inhibits tumor cell proliferation by reducing CD317 expression of tumor cells, reduces PD-L1 expression so as to break the immune escape mechanism, simultaneously enhances the killing sensitivity of tumor cells to CD8+ T cells, forms a synergistic effect with the oncolysis of the oncolytic virus, and the recombinant oncolytic virus has stronger in-vivo anti-tumor activity, thereby providing a new potential scheme for CD317-driven tumor treatment.

The present invention relates to an oncolytic virus co-expressing the complement regulatory proteins CD55 and CD59. The oncolytic virus of the present invention maintains efficacy even upon intravenous injection, and thus, it may be applied to the therapy for various solid carcinomas and metastatic cancers as well as superficial solid cancers. In addition, the oncolytic virus of the present invention acquires resistance to the attack of human complement system by expressing a complement regulatory protein on the surface of the virus, and thus, it is stable in blood, and it maintains stable oncolytic activity upon intravenous injection, and thus, it may reduce the dose of the virus to minimize adverse effects of anticancer agents. Therefore, the oncolytic virus of the present invention may be advantageously used for prevention or treatment of cancer.

This invention relates to gene constructs, expression cassettes comprising said gene constructs, and oncolytic viruses, and their use in methods for treating, preventing, or alleviating cancer. The gene constructs, expression cassettes, and oncolytic viruses are particularly useful (but not limited to) for treating bladder cancer, such as non-muscle-invasive bladder cancer.

The present disclosure provides oncolytic viruses expressing a modulator of interferon regulatory factors (IRFs), and compositions comprising thereof. The present disclosure further provides methods of using said oncolytic viruses and compositions for treating cancer, and for improving a subject's responsiveness to an immunomodulatory agent (e.g., an immune checkpoint inhibitor).

The present invention relates to oncolytic vaccinia viruses and recombinant viruses and methods of use thereof. In particular, the present invention provides a cloned vaccinia virus strain exhibiting enhanced anti-tumor properties and / or reduced immunogenicity, as well as a recombinant vaccinia virus derived therefrom. The present invention also provides recombinant oncolytic virus strains comprising an inactivated mutation in one or more viral genes, and / or one or more heterologous nucleic acids each encoding one or more heterologous gene products. The viruses (e.g., vaccinia viruses, including recombinant vaccinia viruses) provided herein are useful as oncolytic viral therapies (e.g., oncolytic vaccinia viral therapies) for the treatment of cancer. The invention also provides pharmaceutical compositions of the virus, such as vaccinia virus, and methods and uses of the virus, such as vaccinia virus, for the treatment of cancer, as well as nucleic acids encoding the virus.

Compositions and methods are provided that enhance CAR T-cell therapy by providing an oncolytic virus engineered to direct expression and secretion of a multivalent adapter protein. The multivalent adapter protein targets both a broadly tumor-associated cell surface antigen and an antigen binding domain of a CAR T-cell.

This invention relates to oncolytic vaccinia viruses, recombinant viruses thereof, and methods of use. Specifically, the invention provides vaccinia virus clone lines and recombinant vaccinia viruses derived therefrom, said vaccinia virus clone lines exhibiting enhanced antitumor properties and / or reduced immunogenicity. The invention also provides recombinant oncolytic virus lines comprising inactivating mutations in one or more viral genes, and / or one or more heterologous nucleic acids each encoding one or more heterologous gene products. The viruses provided by this invention (such as vaccinia viruses, including recombinant vaccinia viruses) can be used as oncolytic virus therapies (such as oncolytic vaccinia virus therapy) for the treatment of cancer. The invention also provides pharmaceutical compositions of viruses (such as vaccinia viruses), methods and uses of viruses (such as vaccinia viruses) for the treatment of cancer, and nucleic acids encoding said viruses.

A method for treating lung cancer by nebulization is provided, comprising an oncolytic virus preparation for nebulization and a method for treating lung cancer by nebulization of an oncolytic virus, wherein the oncolytic virus is an oncolytic virus expressing interferon.

The application relates to the technical field of biological medicine, in particular to a medicine for combined treatment of tumors by using a recombinant oncolytic virus and a small-molecule anticancer drug. The method comprises the following steps: combined treatment of tumors by using a recombinant oncolytic virus and a small-molecule anticancer drug; the small-molecule anticancer drug is a small-molecule anticancer drug targeting EGFR; the recombinant oncolytic virus comprises M protein, G protein, N protein, P protein and L protein after site-directed mutagenesis. The application can kill tumor cells by using a recombinant oncolytic virus and a small-molecule anticancer drug, and the curative effect is 1+1>2.

The application relates to immunoconjugates for use in a method of treating bladder cancer in a human patient, wherein the method comprises administering the immunoconjugate to the patient, wherein the immunoconjugate comprises: (i) an antibody that binds to PD-1; and (ii) a mutant IL-2 polypeptide comprising the amino acid substitutions F42A, Y45A and L72G. The immunoconjugates are capable of binding in cis to PD-1 and stimulating IL-2 signalling on the same cell, providing selective IL-2 receptor signalling on PD-1 positive T cells relative to the PD-1 negative T cells. The application also relates to the use of the immunoconjugates in combination with immunotherapeutic agent, which is bacterial strain or an oncolytic virus, such as the BCG vaccine.

This invention relates to the field of biomedicine, specifically to an oncolytic virus targeting TIPE2, its preparation method, and its applications. This invention constructs a recombinant expression vector by inserting a TERTp fragment, a TIPE2 shRNA fragment, and a promoter driving the expression of the TIPE2 shRNA fragment into the vector. This achieves effective oncolytic function without affecting normal cell viability, and also effectively silences the expression of the TIPE2 gene in immunosuppressive cells, weakening the immunosuppressive effect in the tumor microenvironment, reshaping the body's anti-tumor immune response, and thus achieving a more effective tumor treatment effect.

The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipids and a self-amplifying replicon RNA comprising a sequence encoding an immunomodulatory molecule.

The present invention relates to the technical field of biomedicine, and in particular to a recombinant oncolytic virus expressing a bispecific or trispecific single-chain antibody, and the use thereof. The recombinant oncolytic virus comprises an antibody gene integrated into a viral backbone thereof. The antibody gene comprises a target antibody gene targeting tumor cells and at least one antibody gene targeting immune cells. The immune cells are selected from any one or two of T cells, NK cells and macrophages. When the antibody gene comprises one target antibody gene targeting tumor cells and one antibody gene targeting immune cells, the antibody gene is a bispecific antibody. When the antibody gene comprises one target antibody gene targeting tumor cells and two antibody genes targeting immune cells, the antibody gene is a trispecific antibody. By means of integrating a gene encoding a bispecific single-chain antibody or a trispecific single-chain antibody into a modified oncolytic virus, the gene for the bispecific single-chain antibody or the trispecific single-chain antibody can be expressed in vivo, thereby further improving the therapeutic effect on tumor cells.

Disclosed in the present application are an immune-activating recombinant oncolytic virus and use thereof, relating to the field of biomedicine. A genome of the immune-activating recombinant oncolytic virus comprises a first nucleotide sequence for encoding an HBsAg molecule, a second nucleotide sequence for encoding an IL-15 molecule, and a third nucleotide sequence for encoding a sushi domain of IL-15Ra. According to the present application, by inserting the first nucleotide sequence for encoding the HBsAg molecule, the second nucleotide sequence for encoding the IL-15 molecule, and the third nucleotide sequence for encoding the sushi domain of IL-15Ra into the genome of the immune-activating recombinant oncolytic virus, the cure rate of tumors is improved while tumor recurrence is prevented.

This invention relates to the preparation and application of an oncolytic virus that specifically promotes the rupture of tumor cell plasma membranes. Specifically, this invention utilizes a glioblastoma-specific Nestin enhancer or a tumor cell-specific Survivin promoter to drive the specific expression of the NINJ1 or DTA gene, thereby enhancing the lytic and killing ability of cells. The oncolytic virus G005 expressing NINJ1 exhibits strong killing ability against tumor cells, and the tumor completely disappears in an orthotopic glioma animal model. It can also rapidly restore the weight loss in mice caused by tumor burden, demonstrating that the oncolytic virus G005 has excellent therapeutic effects against GBM.

Provided are an oncolytic virus, a preparation method therefor, the use thereof and a medicine thereof, wherein the genome of the oncolytic virus includes the following exogenous elements: (1) a first expression cassette containing a first promoter and a first interfering RNA expression sequence; (2) a target sequence; and (3) a second expression cassette. The replication of the oncolytic virus is regulated and controlled by exogenous elements inserted into the genome sequence thereof; by means of the regulation and control by the exogenous elements, the oncolytic virus can be selectively replicated in different types of cells, and thus, second cells, that is, target cells (such as tumor cells), can be selectively killed, and first cells, that is, non-target cells (such as normal cells), are not damaged.

An isolated monoclonal antibody that specifically binds human Siglec15, or an antigen-binding portion thereof. A nucleic acid molecule encoding the antibody or antigen-binding portion thereof, an expression vector, a host cell, and a method for expressing the antibody or antigen-binding portion thereof are also provided. The present disclosure further provides an immunoconjugate, a bispecific molecule, a chimeric antigen receptor, an oncolytic virus and a pharmaceutical composition comprising the antibody or antigen-binding portion thereof, as well as a treatment method using the same.

The present invention relates to the field of oncolytic viruses and in particular to a recombinant rhabdovirus, such as vesicular stomatitis virus encoding in its genome for a gasdermin. The invention is further directed to the use of the recombinant virus in the treatment of cancer and also to methods for producing such viruses.

This application relates to the field of biomedicine, specifically to a drug for the combined treatment of tumors using a recombinant oncolytic virus and a small-molecule anticancer drug. The specific steps include: treating tumors using a combination of a recombinant oncolytic virus and a small-molecule anticancer drug; the small-molecule anticancer drug is a BTK-targeting small-molecule anticancer drug; the recombinant oncolytic virus includes site-directed mutated M, G, N, P, and L proteins. This application utilizes the combined attack and killing of tumor cells by a recombinant oncolytic virus and a small-molecule anticancer drug, achieving a therapeutic effect greater than the sum of its parts (1+1>2).

To provide an effective cancer therapy with reduced side effects (e.g., compared to chemotherapy).SOLUTION: Provided is use of oncolytic viruses (e.g., Talimogene laherparepvec) either alone or in combination with an immune checkpoint inhibitor (e.g., anti-CTLA-4, anti-PD-1 and anti-PD-L1 compounds such as antibodies). In addition, the present invention provides compositions and kits related to such use of oncolytic viruses either alone or in combination with an immune checkpoint inhibitor.SELECTED DRAWING: Figure 11a

This application provides a recombinant oncolytic virus carrying a PD-1 / RGMb bispecific antibody, its preparation method, and its application. The preparation method includes the following steps: S1: preparing the plasmid pXN2-M51R-GFP; S2: obtaining the PD-1 / RGMb bispecific antibody sequence; S3: amplification of the Mouse PD-1 / RGMb bispecific antibody; S4: restriction enzyme digestion of the pXN2-M51R-GFP vector; S5: ligation of the target gene to the vector and transformation of the ligation system; S6: packaging of the recombinant vesicular stomatitis virus; S7: infection of Vero with the recombinant vesicular stomatitis virus; S8: resuspension and extraction of the target virus. In this application, the oncolytic virus is engineered using viral reverse genetics technology to design and construct a tandem PD-1 / RGMb bispecific antibody, which is then integrated into the vesicular stomatitis virus genome. This strategy aims to simultaneously block the PD-1 / PD-L1, PD-1 / PD-L2, and PD-L2 / RGMb signaling axes, thereby reshaping the immunosuppressive tumor microenvironment and synergistically enhancing the oncolytic virus-induced antitumor immune response.

The present application relates to oncolytic viruses reshaping tumor microenvironment and application thereof. Specifically, the present application provides a novel engineered oncolytic virus carrying a coding gene of a fusion protein of dominant negative transforming growth factor-beta type II receptor (DN TGF-beta RII) and IL-10 and anti-PD-1 antibody, which can simultaneously play the effects of regulating tumor microenvironment and activating immune cells, and the action molecules have a prolonged half-life, significantly improving the anti-tumor effect of the engineered oncolytic virus. Experimental results show that the engineered oncolytic virus of the present application exhibits excellent tumor inhibition effect on various tumors, and has a broad application prospect.

The present invention relates to compositions, methods, uses and kits for combination therapies involving immunotherapies, such as adaptive cell therapy, e.g., T cell therapy, and an oncolytic virus (particularly parvovirus H-1), for treating subjects with cancer. The T cell therapy includes cells that express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the cancer is a solid tumor or a hematological malignancy.

This invention belongs to the field of biomedical technology, specifically relating to the application of tryptophan metabolites in enhancing oncolytic virus (OHSV) function. This invention first discovered that fecal bacterial suspensions from healthy individuals enhance the antitumor effect of oHSV treatment. Based on 16S rDNA amplicon sequencing, the invention identified the aforementioned bacterial genus as the dominant genus. Further verification showed that oral administration of these microorganisms in combination with oHSV significantly reduced tumor volume. Identification of the bacterial suspension metabolites revealed that tryptophan metabolites can delay the clearance of OVs by the host cell's antiviral response, increase the replication titer and persistence of OVs within tumors, and promote cytotoxic CD8+ within tumors. + T cell infiltration and anti-tumor immune response.

To provide a method of administering a virus to tumor tissues using an endoscope.SOLUTION: A method of administering a virus to tumor tissues using an endoscope is provided, which comprises inserting an endoscopic puncture needle filled with a virus-containing solution into tumor tissues and injecting the virus into the tumor tissues.SELECTED DRAWING: None

The present invention relates to compositions, methods, uses and kits for combination therapies involving immunotherapies, such as adaptive cell therapy, e.g., T cell therapy, and an oncolytic virus (particularly parvovirus H-1), for treating subjects with cancer. The T cell therapy includes cells that express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the cancer is a solid tumor or a hematological malignancy.

An oncolytic virus for use in a method of treating or preventing cutaneous squamous cell carcinoma (CSCC), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), small cell lung cancer (SCLC), advanced recurrent head and neck cancer, squamous cell carcinoma of the head and neck (SCCHN), nasopharyngeal carcinoma (NPC), hepatocellular carcinoma (HCC), anal cancer, colorectal cancer (CRC), basal cell carcinoma (BCC), Merkel cell carcinoma, appendiceal carcinoma, sarcoma of the skin, recurrent melanoma after surgery, advanced or metastatic urothelial carcinoma, liver metastases, microsatellite instability high cancer (MSI-H), mixed advanced solid tumors, virally caused cancer, locoregionally advanced cancer, pediatric cancer, cancer in patients with no or minimal pre-existing anti-cancer immunity, cancer as first line therapy, cancer in previously treated patients, cancer in patients who have not received checkpoint blockade therapy, and / or cancer in patients who have received checkpoint blockade therapy, wherein the oncolytic virus: is, or is derived from, a clinical isolate which has been selected by comparing the abilities of a panel of three or more clinical isolates of the same viral species to kill tumor cells of two or more tumor cell lines in vitro and selecting a clinical isolate which is capable of killing cells of two or more tumor cell lines more rapidly and / or at a lower dose in vitro than one or more of the other clinical isolates in the panel; comprises (i) a fusogenic protein-encoding gene; and (ii) an immune stimulatory molecule or an immune stimulatory molecule-encoding gene; comprises (i) a GM-CSF-encoding gene; and (ii) an immune co-stimulatory pathway activating molecule or an immune co-stimulatory pathway activating molecule-encoding gene; and / or comprises a gene encoding a CTLA-4 inhibitor.

Provided herein are nucleic acids, vectors, viral particles, and nanoparticles for delivering immunogenic cell death executioners, e.g., a N-terminal domain of gasdermin D (GSDMD) and / or a N-terminal domain of Mixed Lineage Kinase Domain Like Pseudokinase (MLKL) to cancer cells. The immunogenic cell death executioners induce necroptosis and pyroptosis, respectively, and are under the control of cancer- (e.g., epithelial cell and / or mesenchymal cell) specific promoters for treating carcinomas (e.g., breast carcinomas).