168 results about "Oncolytic virus" patented technology

The invention discloses a cell membrane protein replacement type oncolytic virus vector and application thereof. The cell membrane protein replacement type oncolytic virus vector is rhabdoviridae virus, and a nucleotide sequence for coding G protein in a genome of the rhabdoviridae virus is replaced by a nucleotide sequence for coding an antibody and a nucleotide sequence for coding a spike protein truncation of coronavirus. The invention also discloses a construction method of the cell membrane protein replacement type oncolytic virus vector for expressing the antibody, the non-replicated virus vector is used for expressing the antibody sequence for the first time, and meanwhile, the novel coronavirus cell membrane protein is embedded into the virus surface, so that the cell membrane protein replacement type oncolytic virus vector can be rapidly produced in a suspension cell in a large scale; through removal of virus cell membrane protein genes, the virus cell membrane protein genes cannot be continuously replicated in vivo, so that the safety of the virus cell membrane protein genes is ensured, the tumor immunosuppression condition is improved, and an organism can be stimulated to generate a neutralizing antibody for resisting new coronavirus while tumor cells are killed.

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

A method for treating tumors using a combination of an oncolytic virus vaccine and immune cells. The method specifically includes the following step: treating the tumors by using a combination of the immune cells and the oncolytic virus vaccine; the oncolytic virus vaccine includes a recombinant oncolytic virus expressing a tumor antigen and is used for targeting the tumor cells; the immune cells express a chimeric antigen receptor paired with the tumor antigen, and are used for killing or destroying the tumor cells targeted; the recombinant oncolytic virus includes an M protein, G protein, N protein, P protein and L protein subjected to site-directed mutagenesis. The tumor antigen expressed by the oncolytic virus vaccine can guide the immune cells to reach the target tumor tissue center, achieving a curative effect where 1+1 is greater than 2, with a tumor cell killing rate being up to 100% at most.

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 is directed to an oncolytic vector together with one or more antibiotics, one or more a probiotics or other microbiome-targeting compositions, and / or one or more fecal transplant for use in the treatment of cancer. The invention is also directed to a pharmaceutical composition comprising an oncolytic vector with one or more of the following: an antibiotic, a probiotic, a microbiome-targeting composition and a fecal transplant. The invention is also directed to a kit which comprises a first container, a second container, and a package insert, wherein the first container comprises at least one dose of a pharmaceutical composition containing an oncolytic vector, the second container containing one of the following: an antibiotic, a probiotic, a microbiome-targeting composition or a fecal transplant, and the package insert comprises instructions for treating a subject having cancer using the compositions of the first and second containers, wherein said probiotic, microbiome-targeting composition or fecal transplant comprises or promotes a bacterial species which improves the effect of the treatment with an oncolytic vector in a subject when said bacterial species is present in the gut microbiome of said subject, and wherein said antibiotic is effective against a bacterial species which decreases the effect of the treatment with an oncolytic vector in a subject when said bacterial species is present in the gut microbiome of said subject.

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.

Provided is a use of an oncolytic virus in the treatment of pain, especially in the treatment of cancer while relieving cancer pain. The drug effect time of the oncolytic virus for relieving cancer pain is obviously longer than that of the existing opioid analgesic, and the dual effects of treating cancer and easing pain are achieved at the same time.

This application relates to the biomedical technology field, and more specifically to a tumor therapy method combining recombinant oncolytic viruses and small molecule anticancer drugs. Specifically, it includes the step of treating a tumor using recombinant oncolytic viruses and small molecule anticancer drugs in combination, wherein the small molecule anticancer drugs include ALK-targeting small molecule anticancer drugs, BTK-targeting small molecule anticancer drugs, EGFR-targeting small molecule anticancer drugs, FGFR-targeting small molecule anticancer drugs, HER2-targeting small molecule anticancer drugs, Parp-targeting small molecule anticancer drugs, PI3K-targeting small molecule anticancer drugs, VEGFR-targeting small molecule anticancer drugs, CDK4 / 6-targeting small molecule anticancer drugs, and KRAS-targeting small molecule anticancer drugs, and the recombinant oncolytic viruses include site-directed mutagenesis of M protein, G protein, N protein, P protein, and L protein. In this application, it is possible to achieve an effect greater than 1+1 by using recombinant oncolytic viruses and low-molecular-weight anticancer drugs in combination to attack and kill tumor cells.

Provided herein are oncolytic viruses containing payload genes, including genes encoding IL-12, FLT3L, CD40 agonists, and / or CTLA-4 antibodies. Expression cassettes, pharmaceutical compositions, and methods of treatment using these viruses are also provided. Additionally, expression cassettes and CD40 agonist molecules are also provided in the present disclosure.

This disclosure relates to methods for selecting therapy for a subject with glioma, and treating said subject, according to the pretreatment tumor microenvironment, wherein when a tumor from the subject has a high level of similarity with reference samples with low tumor microenvironment, medium tumor microenvironment, or high tumor microenvironment, different therapies are selected, which can comprise an oncolytic virus, a combination of an oncolytic virus and an anti-PD-1 antibody, or a combination of an oncolytic virus, an anti-PD-1 antibody, and at least one additional immune checkpoint inhibitor, respectively.

The invention discloses a bispecific antibody fusion protein, a recombinant oncolytic virus and application of the bispecific antibody fusion protein and the recombinant oncolytic virus in preparation of drugs for treating tumors, the recombinant oncolytic virus can express and secrete a bispecific antibody HER2-BiTE, and the bispecific antibody HER2-BiTE can serve as an adapter to recruit T cell targeted HER2 positive tumor cells, so that the killing effect of the T cells on the tumor cells is improved; meanwhile, the oncolytic virus causes tumor cell lysis, tumor-associated antigen release and tumor microenvironment remodeling; the BiTE plays a role in tumor sites, so that the adverse reaction of systemic administration is relieved. The synergistic effect of the oncolytic virus and the bispecific antibody improves the tumor treatment effect.

The present application relates to the application of an oncolytic virus carrying interleukin 10 in the field of colorectal cancer liver metastasis. The present application provides the use of a recombinant oncolytic virus in the preparation of a drug for treating colorectal cancer liver metastasis, wherein the recombinant oncolytic virus expresses interleukin 10. The recombinant oncolytic virus provided in the present application can overcome the immune clearance of the virus and the immunosuppression of the liver metastasis in the treatment of colorectal cancer liver metastasis, thereby improving the treatment effect of colorectal cancer liver metastasis.

The invention belongs to the field of biological medicine, and particularly relates to application of TPRA1 in the anti-tumor effect of oncolytic viruses. The invention provides the application of the oncolytic virus in preparation of the TPRA1 high-expression tumor medicine and the application of the TPRA1 accelerant in preparation of the oncolytic virus anti-tumor synergist or the drug resistance reversal agent for the first time. On the basis, the application of a substance for detecting the TPRA1 in preparation of products for oncolytic virus anti-tumor curative effect evaluation, oncolytic virus anti-tumor prognosis evaluation, tumor treatment scheme selection and / or tumor diagnosis or prognosis evaluation is provided for the first time; meanwhile, it is proved that the antitumor effect can be remarkably improved through combined medication of the oncolytic virus and the TPRA1 accelerant.

A tumor-targeting protein or a fragment thereof, an antibody binding thereto and a use thereof are disclosed. A vector containing a nucleic acid coding for protein A56 or a fragment thereof, and a use thereof are disclosed. An antibody binding to protein A56 or a fragment thereof, and a use thereof are disclosed. The vector containing A56-encoding nucleic acid, a fragment thereof or a mutant thereof uses an oncolytic virus as the vector, and thus, when administered in an individual, specifically kills only cancer cells, primarily. In addition, cancer cells which have survived even after being infected with the oncolytic virus express the protein A56 on the cell surfaces thereof, and thus may be targeted for secondary anticancer therapy employing protein A56-encoding nucleic acid or protein A56 or a fragment thereof, or an antibody binding to A56.

The disclosure provides Myxoma virus that expresses one or more immunomodulatory transgenes and its use in inhibiting and / or treating a hematological cancer in a subject. The disclosure also provides a leukocyte having a Myxoma virus that expresses one or more immunomodulatory transgenes and the use of the leukocyte for inhibiting and / or treating a hematological cancer in a subject.

Described herein are methods and compositions for treating a disease, e.g. cancer (including solid tumors), using glial cells (e.g. microglia cells and / or astrocytes) and / or macrophages (e.g., CNS-associated macrophages) infected with an oncolytic virus (e.g., vaccinia virus). The methods and compositions provided herein demonstrate a synergistic anti-cancer effect.

The present invention relates to oncolytic virus comprising: (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.

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.

The invention belongs to the technical field of biological medicines, and particularly relates to a membrane-coated oncolytic virus as well as a preparation method and application thereof. The oncolytic virus contains a GSDMD N-terminal expression cassette regulated and controlled by a heated shock promoter, and pyroptosis can be induced under exogenous mild thermal stimulation, so that the virus is promoted to be quickly released, and reinfection and amplification of adjacent tumor cells are realized. A bionic nano-vesicle (iNV) formed by a donor cell membrane modified by genetic engineering is used as an outer layer to coat a genetically engineered oncolytic virus (GOV) to obtain a membrane-coated oncolytic virus iNV-GOV, so that the membrane-coated oncolytic virus iNV-GOV simultaneously has immunocompatibility and active tumor recognition capability, is suitable for solid tumors such as pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHCC) and the like, and can be used for preparing an anti-tumor drug. And the tumor volume can be obviously reduced in mouse in-vivo model experiments.

The present invention relates to compositions and methods for treating cancer utilizing oncolytic viruses, components thereof, and / or derivatives thereof. In particular, the present invention relates to modified picornaviruses that contain alterations in one or more of their capsid proteins that confer enhanced binding ability to cancer cells.

The present invention relates to an oncolytic virus which 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.

The invention discloses a neurotoxicity-free VSV vector recombinant oncolytic virus carrying Marburg virus deficient G protein, which is characterized in that a G protein coding gene of wild VSV is replaced by a coding gene of Marburg virus deficient G protein through a reverse genetic manipulation technology, so as to save and obtain a recombinant oncolytic virus VSV-MARG-delta MLD capable of being autonomously replicated. The invention has the advantages of no neurotoxicity and efficient oncolytic activity.

The present invention provides: an oncolytic virus such as a conditionally replicating adenovirus carrying the CXCL10 gene; the oncolytic virus additionally carrying the IL-2 gene and / or the GM-CSF gene on the same viral genome; a combination of the oncolytic virus and a separate oncolytic virus carrying the IL-2 gene and / or the GM-CSF gene; and a cancer treatment agent comprising any of the aforementioned oncolytic viruses or a combination thereof as an active ingredient.

The present application provides an isolated monoclonal antibody or antigen-binding portion thereof that specifically binds to human IL6R. Also provided are nucleic acid molecules encoding the antibody or antigen-binding portion thereof, expression vectors, host cells, and methods for expressing the antibody or antigen-binding portion thereof. The present application also provides bispecific molecules, immunoconjugates, chimeric antigen receptors, oncolytic viruses, and pharmaceutical compositions comprising the antibody or antigen-binding portion thereof, as well as therapeutic methods using the IL6R antibody or antigen-binding portion thereof.

Provided are an oncolytic virus preparation capable of crossing a blood-brain barrier, a preparation method therefor and a use thereof. The oncolytic virus preparation is an oncolytic virus modified by a polypeptide having a function of crossing a blood-brain barrier. The polypeptide having the function of crossing the blood-brain barrier is RVG29-Cys. The oncolytic virus is a genetically engineered oncolytic virus OH2 in which neurotoxic and immunosuppressive genes in a wild-type virus genome are knocked out and an immune-enhancing human granulocyte-macrophage colony stimulating factor gene is inserted. An OH2-PEG-RVG nanosystem is constructed by conjugating NHS-PEG-Mal to OH2, and then coupling a Mal group on NHS-PEG-Mal to a Cys group on RVG29-Cys, thus increasing the aqueous solubility of a drug while facilitating the therapeutic drug crossing of the blood-brain barrier to treat brain tumors, and preventing neutralizing antibodies and macrophages in vivo from neutralizing and phagocytosing the oncolytic virus, thereby prolonging the circulation time in vivo.

The application provides a recombinant oncolytic virus targeting a tumor hypoxic microenvironment and an application thereof. A genome of the recombinant oncolytic virus comprises at least one nucleic acid fragment selected from a first nucleic acid fragment, a second nucleic acid fragment and a third nucleic acid fragment; wherein the first nucleic acid fragment comprises genes encoding an immunosuppression relief and T cell local activation unit and genes encoding a T cell function enhancement and chemotactic expansion unit; the second nucleic acid fragment comprises genes encoding a hypoxia sensing unit and genes encoding a T cell activation antibody expression unit; and the third nucleic acid fragment comprises at least one gene encoding an immunomodulatory unit. The recombinant oncolytic virus has three action mechanisms of a high remodeling of a solid tumor microenvironment, a universal in vivo T cell adapter and a virus conditional replication regulation, and can be effectively used for tumor treatment.

Described herein, inter alia, are oncolytic viruses expressing a truncated human BCMA (BCMAt) and methods for treating a patient suffering from a solid tumor by administering an oncolytic virus expressing a truncated human BCMA and a BCMA-targeting therapy (e.g., a protein that binds a BCMA antigen, T cell engager targeted to BCMA, BCMA CAR immune cells, anti-BCMA antibody or antibody fragment).

The invention belongs to the technical field of biological medicine, and particularly discloses a complex tumor organoid co-culture system and a construction method and application thereof. The construction method comprises the following steps: construction of tumor organs, separation and induced differentiation culture of dendritic cells, fusion of tumor cells and maturely differentiated dendritic cells (DCs) through oncolytic viruses, and addition of immune cells for co-culture. According to the present invention, the patient-derived tumor cells are utilized to construct the tumor organoid, such that the pathological characteristics of the patient can be well restored; the oncolytic virus is used for inducing fusion of the dendritic cells and the primary tumor cells, so that related antigens, specific antigens and new antigens of the tumor cells can be presented more effectively, and the reaction of immune cells can be stimulated more efficiently; the rapid, simple and effective complex tumor organoid co-culture established by the invention can simulate the positioning and interaction relationship between immune cells and tumor cells in an in-vivo tumor microenvironment, and also provides a platform for evaluation of a novel immunotherapy.