71results about "Liver cancer vaccine" patented technology

A specific chimeric antigen receptor targeting NKG2DL, its coding sequence, and modified immune response cells, as well as their preparation method and application. The modified immune response cells can effectively target and attack various tumor cells, especially positive tumor cells expressing NKG2DL, and can be used to prepare preparations for treating tumors.

The invention discloses a double-chimeric antigen receptor, a T cell and a construction method and an application thereof, which belong to the field of cellular immunotherapy of tumors. The inventionspecifically relates to a specific structure and a construction method of the double chimeric antigen receptor T cell (dCAR-T cell), and preliminarily discusses the in-vivo and in-vitro activity of the dCAR-T cell. The selected tumor-associated antigens are mesothelin and carcino-embryonic antigens, and researches show that the two tumor antigens can be simultaneously expressed on the surface of asolid tumor, such as pancreatic cancer. The invention discloses an antigen receptor. The in-vitro and in-vivo tests prove that the constructed dCAR-T cell can be permanently and effectively activatedonly under the condition that two antigens are simultaneously recognized, and has efficient anti-tumor activity, so that a specific tumor killing function can be exerted, and the application of CAR-Tcell immunotherapy is improved.

The invention relates to an antigen and adjuvant co-delivery nanometer vaccine applied to liver cancer immunization therapy. Sodium alginate and polymine are used as carrier materials, liver cancer specific polypeptide antigen phosphatidylinositol proteoglycan 3127-136 peptides(GPC3127-136, AMFKNNYPSL) are used as immunizing antigens, CpG oligodeoxynucleotide is used as an adjuvant, and through static electricity interaction, the antigen and adjuvant co-delivery nanometer vaccine is prepared, wherein the mass ratio of the carrier materials to the immunizing antigens to the adjuvant is 1: (1-10): (0.3-0.8). The nanometer vaccine disclosed by the invention can increase the endocytosis quantity of dendritic cells (dendritic cell, DC) to the antigen and the adjuvant, and through raising costimulatory molecules on the surfaces of the DCs and promoting the secretion of cytokine of TNF-a, IL-6 and the like, arousing organisms to produce effective immune response is facilitated; and besides, the raw materials are cheap and easy to obtain, the preparation method is easy and easily repeated, large-scale processing and producing are easy, the liver cancer immunization therapy effects can be strengthened, and the antigen and adjuvant co-delivery nanometer vaccine has favorable application prospects.

The invention discloses an ROBO1 CAR-NK cell carrying a suicide gene as well as a preparation method and application of the ROBO1 CAR-NK cell. In order to improve the safety and controllability of theCAR-NK therapy, a suicide gene switch element is integrated into a genome through a lentiviral transfection technology on the basis of the current ROBO1 CAR-NK cell to form the CAR-NK with the suicide gene. By adding the suicide gene, the CAR-NK cells can be better controlled, and the clinical safety is further improved.

The invention relates to chimeric antigen receptor T cell (CAR-T) in the treatment of hepatocellular carcinama (HCC) by targeting hepatitis B virus (HBV) and an application thereof. In order to overcome a potential multiple organ off-target effect in the existing CAR-T treatment of HCC, the inventor, after repeated screening, prepares chimeric antigen receptor T cells targeting HBV surface antigen (HBVsAg). The results show that CAR-T prepared in the invention has a good killing effect on HBV positive HCC cells, and has a significantly higher killing effect than the CAR-T cells targeting GPC3 in current clinical trials and researches, showing a better application prospect.

The invention discloses a chimeric antigen receptor of a cell for targeted expression of Claudin 18.2 (CLDN 18.2), and particularly discloses a chimeric antigen receptor with an amino acid sequence as shown in SEQ ID NO.14. The chimeric antigen receptor comprises a Claudin 18.2-targeted single-chain antibody, a hinge region, a transmembrane structural domain and an intracellular signal structural domain. The Claudin 18.2-targeted chimeric antigen receptor disclosed by the invention can achieve effective and specific targeted expression of malignant cells (such as tumor cells) of the Claudin 18.2 surface antigen, so that a more efficient method with fewer side effects and adverse reactions is provided for treating some tumors expressing the Claudin 18.2 surface antigen.

The invention provides a composition of a DC vaccine and an NKG2A antagonist and application of the composition in anti-breast cancer or liver cancer. The DC vaccine in the composition is different from the early traditional tumor cell full-antigen-loaded DC vaccine, has specific targeting antigens, can more accurately treat tumors and reduce the killing side effects on normal cells; and secondly,the composition further contains a novel immune checkpoint inhibitor NKG2A antagonist which enables tumor cells with CD94-NKG2A / HLA-Ereceptor-ligand on the surface to be recognized and killed by NK cells and T cells, and an antigen presentation function of dendritic cells is enhanced, so that some cells which are not subjected to presentation and antigen by the DC vaccine are captured by an immune system again, the treatment effect on breast and liver cancer is enhanced, effect is faster than the conventional DC vaccine, the time of duration is longer, and the immunotherapy process is promoted.

The invention discloses a chimeric antigen receptor T lymphocyte and an application thereof to preparation of a product for treating solid tumors. A chimeric antigen receptor in the chimeric antigen receptor T lymphocyte sequentially comprises a human CD8 lead peptide, an anti-Siglec-15 single-chain antibody, a human CD8 hinge transmembrane region, a human 4-1BB intracellular region, a human CD3 zeta intracellular region, a self-cleavage peptide, a CSF2Ra signal peptide, an EGFRt protein, a self-cleavage peptide and a human CD27. Experiments prove that the chimeric antigen receptor T lymphocyte provided by the invention highly expresses IFN gamma and CD107a, has a strong killing function on Siglec-15 positive tumor cells, and has killing efficiency of more than 80% under the condition thatthe effect-target ratio is 1: 1. A tumor transplantation model experiment shows that the chimeric antigen receptor T lymphocyte also has a strong killing function on Siglec-15 positive tumor cells inan animal body.

The invention relates to a multi-signal embedded antigen receptor and an expression gene thereof, an NK (Natural Killer) cell modified by the multi-signal embedded antigen receptor and application. The embedded antigen receptor comprises a first segment, a second segment and a self-pyrolysis polypeptide T2A for connecting the first segment and the second segment, wherein the first segment comprises a first signal peptide, a TCRgamma chain and a TCRdelta chain, which are connected in sequence; the second segment comprises a second signal peptide SP, a tumor antibody, a CD8 structure domain, a 41BB intracellular domain and a DAP12-ITAM structural domain, which are connected in sequence; a C end of the self-pyrolysis polypeptide T2A is connected with the TCRdelta chain; an N end of the self-pyrolysis polypeptide T2A is connected with the second signal peptide SP. An experiment result shows that the multi-signal embedded antigen receptor can be stably expressed in the NK cell and can be used for more rapidly and specifically identifying malignant tumor cells and killing the malignant tumor cells, and the toxic side effect of treatment is reduced.

The invention provides a preparation method of bispecific antibody NK cells, and cells and application thereof. The method comprises the following steps of: culturing NK cells, constructing a CD16A / HSP70 bispecific antibody lentiviral expression vector, and infecting the NK cells by the CD16A / HSP70 bispecific antibody lentiviral expression vector so as to obtain the bispecific antibody NK cells ofa CD16A / HSP70 antibody. The NK cells prepared by the invention are excellent in cell-specific phenotype and high in purity, wherein CD3-CD56+ achieves 97.13%; CD3-CD56+CD16+ achieves 93%; and the NKcells carrying the CD16A / HSP70 bispecific antibody lentiviral expression vector can effectively eliminate liver cancer cells and inhibit increasing of the tumour volume of the liver cancer.

The invention provides a chimeric antigen receptor. The chimeric antigen receptor comprises a GPC3 antigen binding structural domain, an ICD1, ICD2 or ICD3 intracellular signal stimulation domain withamino acid sequences of SEQ ID NO.29, 31 and 33 and IL-15-IL-15alpha fusion protein with an amino acid sequence of SEQ ID NO.7. After the chimeric antigen receptor is transferred into immune cells, especially iNKT cells, the cell proliferation speed, the survival time and the tumour killing effect can be effectively improved. The invention further provides a corresponding expression vector, a transduction system, pharmaceutical application, independent ICD1, ICD2 and ICD3 intracellular signal stimulation domains and IL-15-IL-15alpha fusion protein.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The invention discloses a dual-target chimeric antigen receptor and an expression vector and application thereof, and belongs to the field of tumor immunity medicines. The dual-target chimeric antigenreceptor comprises: a signal peptide, a receptor NKG2D extracellular region targeting NKG2DL, a single-chain antibody targeting GPS3, an elongated CD8 alpha hinge region, a transmembrane region, a co-stimulatory factor and an intracellular signal domain sequentially connected, wherein the signal peptide has a nucleotide sequence as shown in SEQ ID NO: 1 in Sequence Listing, the receptor NKG2D extracellular region has a nucleotide sequence as shown in SEQ ID NO: 2, the single-chain antibody has a nucleotide sequence as shown in SEQ ID NO: 3, the elongated CD8 alpha hinge region has a nucleotide sequence as shown in SEQ ID NO: 4, the transmembrane region has a nucleotide sequence as shown in SEQ ID NO: 5, and the intracellular signal domain has a nucleotide sequence as shown in SEQ ID NO: 6. The dual-target chimeric antigen receptor can avoid a problem of escape of tumor cells with low abundant antigen expression, thereby effectively reducing risk of tumor recurrence.

The invention relates to the technical field of biological cells, in particular to a preparation method and application of high-purity universal CART. According to the preparation method, expression rate of CAR of the universal CART is 100%. The preparation method utilizes crispr-cas9 technology to knock out TRAC and HLA-I B2M genes of T cell TCR to prepare the universal CAR-T, enables expressionrate of CAR of the universal CAR-T to reach 100%, and reduces amount of CAR(-)TCR(-)T cells infused into a human body, thereby reducing unknown risk.

The invention relates to the technical field of immunotherapy or vaccine prevention and treatment, in particular to a heterocyclic compound containing two or more sulfur atoms and an application of the heterocyclic compound to preparation of a nano vaccine. The invention provides an application of the heterocyclic compound which contains at least two sulfur atoms and can be covalently or non-covalently connected with polypeptide to preparation of the nano vaccine. Nanoparticles prepared by self-assembly of the compound and an antigen can enter dendritic cytoplasm in a transmembrane mode, and the uptake efficiency of the antigen and an immunologic adjuvant is improved. In the process of entering the cells, biodegradation of an enzyme body in lysosome on antigens or nucleic acid adjuvants can be effectively avoided or reduced, so that the nano vaccine disclosed by the invention can efficiently activate the dendritic cells and improve the cross presentation effect on the antigens, further CD8 + T cells can be effectively activated, and proliferation of the T cells can be promoted. Therefore, the nano vaccine provided by the invention can prevent tumor cell proliferation and virus infection by utilizing efficient immune activation and immune regulation effects.

The invention discloses a PD-L1 CAR structure, a specific structure of a CAR sequence of the PD-L1 CAR structure is as follows: a CD8 alpha leading peptide-PD-L1 scFv-CD8 alpha transmembrane region, aCD137 intracellular costimulatory domain, a CD247 intracellular activation domain. Tumor targeting and T cell double-activation pathway molecules are integrated into a single PD-L1 chimeric receptorgene, so that the feasibility of treating solid tumors by genetically modified T cells is greatly improved, the preparation cost is reduced, and the product can be applied to treatment of PD-L1 high-expression solid tumors, such as lung cancer, liver cancer, colon cancer and the like.

The present invention belongs to the field of biotechnology and pharmaceuticals. The present inventors found a sequence motif for identifying potent RIG-I agonists. Accordingly, the present invention is directed to a method for producing RIG-I agonists, the RIG-I agonists produced by said methods, and uses of said RIG-I agonists, as defined in the claims.

The present disclosure provides a chimeric antigen receptor and a combination of the chimeric antigen receptor and DAP10. The present disclosure provides an expression vector and a host cell for expressing the chimeric antigen receptor and said combination of the chimeric antigen receptor and DAP10. The present disclosure also provides use of the chimeric antigen receptor and the combination of the chimeric antigen receptor and DAP10 in the treatment of cancers or in the preparation of pharmaceutical compositions for treating cancers. The chimeric antigen receptor and the drugs provided in the present disclosure can effectively treat liver cancer, lung cancer and the like.

The invention discloses a synergistic and depletion-resistant chimeric antigen receptor T cell and application thereof in preparation of a medicine for treating tumors. The synergistic and depletion-resistant chimeric antigen receptor T cell comprises an antigen binding structural domain (scFv) and a signal transduction structural domain, wherein the signal transduction structural domain comprises a first transduction structural domain and a second transduction structural domain, and the antigen binding structural domain is connected in series between the first transduction structural domain and the second transduction structural domain; the first conduction structural domain comprises a receptor signal structural domain and / or a costimulatory structural domain; the second conductive domain comprises a transmembrane structural domain DAP12, and the transmembrane structural domain DAP12 is or is not linked to the costimulatory structural domain and / or an elementary signal domain. According to the T cell expressing the chimeric antigen receptor, the chimeric antigen receptor can be more efficiently and stably expressed in the T cell, so that a killing effect on a target cell can be better played, the durability of CAR-T is improved, the expression of a depletion marker is lower, and the memory type T cell is richer.

The invention relates to a specific chimeric antigen receptor cell armed with a targeted CXCR2 ligand as well as a preparation method and application thereof. Through a method, which uses a recombinant carrier of a chimeric antigen receptor that specifically targets human NKG2DL armed with a targeting CXCR2 ligand to modify a immune response cell, the obtained novel functionalized immune responsecell can effectively attack multiple tumors in a targeted mode; and the functionalized immune response cell can be used to prepare preparations for treating malignant tumors. The engineering immune cells modified by a chimeric antigen receptor that is armed with a targeting CXCR2 ligand and specifically targets human NKG2DL can more easily migrate to a tumor position and continuously kill the tumors in a targeted mode.

The invention provides preparation and application of a retinoic acid induced protein 16 (RAI 16) specific polyclonal antibody.

The invention discloses an immune enhancer, which at least includes interferon and granulocyte-macrophage colony-stimulating factor, and an immunotherapy pharmaceutical composition, which at least includes an antigen and the above-mentioned immune enhancer. The invention also discloses the preparation method of the immunotherapy pharmaceutical composition, the application of the above immune enhancer and immunotherapy pharmaceutical composition. The immunopotentiator provided by the invention can significantly improve the immune ability of the body, improve the antigen presentation efficiency of the body, and enable the body to establish effective immune activation and response; produce stronger antibodies and cellular immune protection responses and the ability to remove pathogens, can It is used in the treatment of diseases and tumors caused by microorganisms such as viruses and bacteria.

The invention belongs to the technical field of gene engineering, and particularly relates to a bispecific single-chain antibody, a CAR structure containing the bispecific single-chain antibody, an expression vector, an immune cell and application. In the single-chain antibody, the amino acid sequence of a Linker1 structure is shown as SEQ ID NO:17 or a functional variant thereof; the amino acid sequence of a Linker2 structure is shown as SEQ ID NO:18 or a functional variant thereof; the Linker1 is connected with a heavy chain variable region of ScFv1 and a light chain variable region of ScFv2 or is connected with a heavy chain variable region of the ScFv2 and a light chain variable region of the ScFv1; and the Linker2 is connected with the light chain variable region of the ScFv2 and the heavy chain variable region of the ScFv2. The construction of the CAR structure overcomes the technical effect defect of a double-target CAR in the prior art; two different tumour antigens can be targeted at the same time; the killing rate of tumour cells is improved; and the immune escape probability of the tumour cells is reduced.