56 results about "INKT Cells" patented technology

The invention relates to a culture method for activating NKT cells by DC cells in vitro and application of the NKT cells. The preparation method of the NKT cell comprises the following steps: activating a DC cell by using cell inducing factors such as alpha-GalCer, GM-CSF and IL-4, co-culturing the DC cell and a cryopreserved and resuscitated suspension cell left after adherent sorting, and activating and amplifying the NKT cell. The proportion of NKT (CD3 + CD56 +) prepared by the invention is more than 80%, and a small amount of iNKT cells are contained at the same time.

The invention relates to invariant natural killer T (iNKT) cells, and particularly, although not exclusively, to iNKT cell engagers or fusion proteins, which specifically bind to iNKT cells. The invention extends to nucleic acids encoding such iNKT cell engagers, as well as novel pharmaceutical compositions comprising these engagers, and to their use in therapy, as well as therapies and methods for treating, preventing, or ameliorating cancer.

The invention discloses a protein variant combination for improving the immune function of iNKT cells and application, and relates to the technical field of tumor immunity. Comprising a protein variant combination consisting of a protein variant ANT A3, a protein variant GLUT3G1, a protein variant LDHB B2, a protein variant PC P4 and a protein variant PCK1K2; according to the invention, gene sequences of the five protein variants are simultaneously embedded into an iNKT cell genome in a fixed-point manner for the first time to form a metabolic reconstitution MetaR-iNKT cell, and it is found that when the MetaR-iNKT cell and an ATP mitochondrial transporter protein inhibitor PENAO are combined for use, lung cancer solid tumors can be synergistically and better killed.

The invention relates to the technical field of cell biology, in particular to an iNKT cell cryopreservation solution and a method for cryopreserving iNKT cells by using the cryopreservation solution. The invention provides an immune cell cryopreservation solution. The immune cell cryopreservation solution comprises human serum albumin, a basic low-temperature protection solution and an optional human platelet lysate. The immune cell freezing medium does not contain animal-derived components except for human bodies, and has the advantages of simple components and good stability. According to the cryopreservation liquid disclosed by the invention, through the combined action of the basic low-temperature protection liquid (such as CryoStor10 (CS10)) and the human serum albumin, the motility rate after cell recovery is improved, and the damage to immune cells (such as iNKT) in the cryopreservation process is reduced. After a small amount of human platelet lysate is further added, the survival rate of cell resuscitation and the amplification capacity can be further improved.

Provided are chimeric ILT receptors (CIRs) that include a targeting region from ILT2 or ILT4, a transmembrane domain, and an intracellular domain (ICD). The ICD includes a signaling region (e.g., CD3 zeta (CD3ζ), DAP10, DAP12) and optionally a costimulatory region (e.g., MyD88, a TIR domain, and the like). Also provided are nucleic acids (e.g., expression vectors) encoding a subject CIR, and genetically modified cells (e.g., immune cells such as NK cells, NK-T cells, T cells, iNKT cells, macrophages, and the like) expressing a subject CIR.

The invention discloses a preparation method of a silicon dioxide nano vaccine for mediating constant natural killer T (iNKT) cells and application of the silicon dioxide nano vaccine in the field of tumor immunotherapy. The iNKT cell is a special T cell subset which can be activated by a glycolipid antigen presented by CD1d, and can directly kill tumor cells and activate other immune cells. Clinically, the classical agonist alpha GC of the iNKT cell can lead to function depletion of the iNKT cell after multiple intravenous administration, and finally evolves into an inactive state. Although the CD1d / alpha GC protein complex relieves the iNKT cell anenergetic state to a certain extent, the CD1d / alpha GC protein complex is easily degraded and cleared in a complex physiological environment, and the treatment effect is weakened. The characteristics of large aperture and high specific surface area of dendritic mesoporous silica are utilized, CD1d / alpha GC is loaded into a pore channel of a mesoporous nano-material, and the design can protect protein drugs from being degraded in blood circulation, so that a nano-vaccine capable of effectively mediating iNKT cells and successfully relieving the inability of the iNKT cells is constructed; and the effectiveness of the compound in tumor treatment is verified. The patent is supported by the national natural science fund (82001958).

A modified iNKT cell, which, compared with an unmodified iNKT cell, lacks or inhibits the expression of a negative immunoregulatory gene, wherein the gene is selected from one or more of the group consisting of PD-1, Tim-3, CTLA-4, CD74 and TGF-βR, and the lack or inhibition of the expression of the negative immunoregulatory gene is realized by means of the technique of intracellular retention / degradation of a membrane protein. Further provided is the use of the iNKT cell and a composition thereof.

We have discovered that allogeneic HSC-engineered human iNKT (3rdHSC-iNKT) cells display potent anti-GvHD functions, by eliminating antigen-presenting myeloid cells in vitro and in xenograft models, without negatively impacting tumor eradication by allogeneic T cells in preclinical models of lymphoma and leukemia. The 3rdHSC-iNKT cells closely resembled the CD4−CD8− / + subsets of endogenous human iNKT cells in phenotype and functionality. Embodiments of the invention harness these discoveries in new methods and materials for alleviating graft versus host disease.

The present application discloses a screening method for tumor immunotherapy reagents targeting Vam6, which comprises administering a candidate reagent to iNKT cells, and treating the iNKT cells with and without the reagent with an iNKT cell activator, and measuring the expression level of Vam6 of the iNKT cells, wherein a decrease or increase in the expression level of Vam6 of the iNKT cells administered with the candidate reagent compared with the iNKT cells without the candidate reagent indicates that the candidate reagent is a potential tumor immunotherapy reagent targeting Vam6. The present application also discloses a method for screening reagents for enhancing the anti-tumor function of iNKT cells using the screening method, and a pharmaceutical composition for treating tumors, which comprises the screened candidate reagent, and a kit comprising the pharmaceutical composition.

The present disclosure relates, at least in part, to compositions comprising constant natural killer T (iNKT) cells (e.g., unmodified allogeneic iNKT cells), and uses of the compositions comprising the iNKT cells to treat a disease or a symptom or complication of a disease (e.g., a viral infection, a disease secondary to a primary disease (e.g., a neurological disease). The present invention relates to a method for treating acute respiratory distress syndrome (ARDS) and / or organ failure associated therewith (e.g., viral infection).

The present application relates to the technical field of biological medicine, and particularly relates to application of PGC-1 alpha activator in preparation of anti-tumor drugs. The present application firstly finds that the PGC-1 alpha activator (such as ZLN005) alone can promote the mitochondrial function and IFN-gamma production of tumor-depleted and disabled iNKT cells, improve the proportion of iNKT and CD8 T cells in the tumor microenvironment, and then improve the tumor microenvironment and inhibit tumor growth. The anti-tumor effect of the PGC-1 alpha activator combined with the NKT cell antigen is more obvious. The present application provides a new scheme for tumor immunotherapy, and provides a new drug target for treatment of other iNKT cell dysfunction diseases, and has important clinical application prospect and value.

The present disclosure relates to compositions comprising constant natural killer T (iNKT) cells, and methods of treating cancer using the compositions comprising the iNKT cells.

The present application relates to a method for preparing iNKT cells. The method comprises the steps of dividing human peripheral blood mononuclear cells (PBMCs) into two parts, then culturing one part by using a culture medium containing one or more iNKT cell agonists, and mixing cells of the two parts.

The present disclosure relates to compositions comprising allogeneic invariant natural killer T (iNKT) cells, including allogeneic iNKT cell adjuvants, and methods of using the compositions comprising the iNKT cells for treatment of diseases and conditions, including cancer.

The present invention relates to a method for mass proliferation and culture of iNKT cells, iNKT cells produced by the method, and uses thereof, the method comprising the steps of: expanding iNKT cells from peripheral blood mononuclear cells; and mass-proliferating and culturing the iNKT cells by treating same with an anti-CD28 antibody, the CD40 protein, and an anti-TCR Vα24-Jα18 antibody. Since the method for mass proliferation and culture of the present invention can produce iNKT cells while maintaining an excellent proliferation rate and purity without artificial antigen-presenting cells, the method can be effectively utilized in related technical fields such as treatment of cancer or inflammatory diseases using iNKT cells.

The present invention relates to: a method for producing immunocytes, specifically induced natural killer T (iNKT) cells that are induced by direct reprogramming of isolated somatic cells, and chimeric antigen receptor (CAR)-iNKT cells into which a CAR gene encoding a CAR is introduced; iNKT cells produced by the method; and a cell therapy composition and a pharmaceutical composition for preventing or treating cancer, comprising the iNKT cells.The method according to the present invention can produce, through direct reprogramming, iNKT cells or iNKT cells into which a CAR gene is introduced, from isolated cells so as to simplify the production process and shorten production time, thereby reducing costs, to have excellent NKT cell production efficiency, and to ensure safety according to the production without passing through induced pluripotent stem cells, thereby having an excellent NKT cell production effect distinguished from that of a conventional reprogramming technique. In addition, the iNKT cells or iNKT cells into which a CAR gene is introduced, which are produced by the method, have an excellent cancer cell killing ability, and thus can be effectively used as a cell therapy composition or a pharmaceutical composition for preventing or treating cancer.

Provided are novel compositions comprising natural killer T cells ("NKT cells") and T cell engagers. In certain embodiments, NKT cells are allogeneic invariant natural killer T cells ("iNKT cells") and the T cell engager is a bispecific or multispecific antibody comprising a CD3 binding domain and a tumor antigen binding domain. The invention includes methods of treating cancer comprising administering to a subject in need NKT cells (e.g., allogeneic iNKT cells) and a T cell engager.

The invention discloses an iNKT cell Th1 type agonist dosization prediction model based on a pre-training model and priori knowledge, and belongs to the technical field of data processing. According to the model, a Gemini mol molecule pre-training model and a molecule docking result are combined, and a relation between iNKT cell Th1 tendency immune response biological activity data and molecules is established through a small sample training model, so that quantitative prediction of Th1 type immune response is realized. The method comprises the following steps: (1) constructing a data set; and (2) activating screening of key amino acid residues in an iNKT cellular immune response target proteome. And (3) analyzing the molecular docking based on AutoDock4GPU and the interaction based on the PLIP library. And (4) constructing a Th1 type immunoreaction small sample transfer learning model based on the pre-training model and priori knowledge. By utilizing the pre-training model and priori knowledge, the Th1 type immune response capability of the glycolipid antigen molecules to the iNKT cells can be effectively predicted, and more efficient Th1 type immune response promoting glycolipid antigen effect evaluation is realized.

The invention relates to a conjugate of a dual agonist and a carbohydrate antigen, the conjugate contains the dual agonist and the carbohydrate antigen, the dual agonist is an iNKT cell agonist and a mincle receptor agonist, the iNKT cell agonist is an alpha-galactosylceramide analogue, and the mincle receptor agonist is a trehalose derivative; the structural general formula of the conjugate is as shown in formula (I): # imgabs0 # X is a carbohydrate antigen, and Y is a linker. The vaccine prepared from the conjugate can activate iNKT cells and mincle receptors at the same time, induce generation of high-titer IgG antibodies and effectively improve the immunogenicity of carbohydrate antigens, and has a good anti-tumor application prospect.

The invention provides a method for in-vitro amplification and induced activation of iNKT cells, and belongs to the technical field of immune cell preparations. The in-vitro amplification method comprises the following steps: S1, separating peripheral blood PBMCs cells; s2, adding a part of PBMCs into a culture medium I for stimulation culture and irradiation, and separating to obtain irradiated PBMCs; s3, re-suspending the other part of PBMCs cells in a culture medium II, adding alpha-GalCer and IL-2 to stimulate culture, then adding the irradiated PBMCs cells, and amplifying iNKT cells; the induction and activation method comprises the following steps: amplifying the iNKT cells, adding a culture medium III, adding a dasatinib derivative, and inducing the iNKT cells to be mature. According to the method, amplification and induced activation of the iNKT cells can be rapidly promoted, the amplification efficiency is high, the obtained iNKT cells are high in cytotoxicity, the method is safe, and graft versus host reaction is not caused.

The present invention relates to an iNKT-TCR molecule, TCR-T cell, preparation and application targeting a lipid antigen and CD1d complex, and belongs to the field of genetic engineering and immunotechnology. The present invention utilizes specific iNKT amplification technology to amplify and sort iNKT cells, and obtains iNKT cell-enriched TCRs by sequencing analysis. In this study, iNKT cells were amplified by iNKT cell-specific activators, high-purity iNKT cells were obtained by magnetic bead sorting, and iNKT cell-enriched TCRs were accurately screened out based on sequencing analysis to ensure their accuracy and specificity. The NKT38 of the present invention has a higher killing effect on tumor cells that express CD1d and present endogenous lipid antigens, and has strong specificity: in vitro experiments show that iNKT-TCR-transfected NKT38 cells have a stronger killing effect on tumor cell lines that express CD1d and present endogenous lipid antigens, suggesting that it has a specific killing effect on tumors.

The present disclosure, at least in part, relates to compositions comprising invariant natural kill T (iNKT) cells (e.g., unmodified, allogeneic iNKT cells), and methods of using the compositions comprising the iNKT cells for treating a disease, or a symptom or complication of a disease (e.g., viral infection, acute respiratory distress syndrome (ARDS) secondary to a primary disease (e.g., viral infection) and / or its associated organ failure).

The invention belongs to the technical field of protein functions and application, and particularly relates to application of TIPE2 protein in preparation of a preparation for inhibiting iNKT cell activation, and a nucleotide sequence for coding the TIPE2 protein is shown as SEQ ID NO.1. The TIPE2 protein provided by the invention can prevent excessive activation of iNKT cells to avoid further autoimmune diseases. The key effect of the TIPE2 in liver related diseases is expanded, and the unknown value of the TIPE2 in the iNKT cell biological function of immune-mediated liver injury is disclosed. It is proved that the TIPE2 is a key regulatory factor of liver homeostasis, and a clue is provided for the TIPE2 to become a potential therapeutic target for regulating immune-mediated liver injury.

The present invention provides a culture medium for inducing type C1 iNKT cells, a culture method thereof and applications thereof, relating to the technical field of cell culture. The culture medium comprises a DC culture medium and an iNKT culture medium. The DC culture medium comprises GM-CSF, IL-4, TNF-α, LPS, 7DW8-5 and autologous plasma. The iNKT culture medium comprises IL-2, IL-7, IL-15, IL-21, 7DW8-5, lupeol, betulinic acid, resveratrol and autologous plasma. Meanwhile, a culture method corresponding to the culture medium is also provided. The type C1 iNKT cells obtained after being cultured with the culture medium of the present invention for 14 days can secrete a relatively high level of IFN-γ without the stimulation of target cells, and the proportion of type C1 iNKT cells in CD3+ T cells increases significantly. Such a culture medium and a culture method can be used in the fields of inducing the growth and expansion of type C1 iNKT cells, exosome extraction, etc., so as to efficiently obtain target cells and target factors.

Lipid nanoparticles (LNP) having an immune regulation function, presenting at least one immune ligand on the surface thereof, promoting activation of non-variant natural killer T cells (iNKT cells) and inducing an immune response, or mediating recognition, binding or internalization between the lipid nanoparticles and the immune cells, and regulating the functional state of the immune cells; the formulation of the lipid nanoparticles comprises at least one of a ceramide-based glycolipid family, a peptidomimetic, and fucosterol, and the formulation forms nanoparticles of 1-1000 nm by a mixing process. The invention provides a lipid nanoparticle formula for enhancing organ targeting, cell targeting or cell activity, a pharmaceutical composition prepared by using the formula and application of the pharmaceutical composition. The formulation can encapsulate and deliver active ingredients such as nucleic acids, gene editing system components and natural small molecules.

The invention relates to an iNKT-TCR molecule of a targeted lipid antigen and CD1d compound, a TCR-T cell and preparation and application, and belongs to the technical field of genetic engineering and immunity. According to the invention, the specific iNKT amplification technology is utilized to amplify and sort the iNKT cells, and the TCR enriched with the iNKT cells is obtained by sequencing analysis. According to the research, iNKT cells are amplified through an iNKT cell specific activator, high-purity iNKT cells are obtained through magnetic bead sorting, TCRs enriched with the iNKT cells are accurately screened out according to sequencing analysis, and the accuracy and specificity of the TCRs are guaranteed. The NKT38 provided by the invention has a higher killing effect on tumor cells expressing CD1d and presenting endogenous lipid antigens, and has very strong specificity: in-vitro experiments show that the iNKT-TCR transfected NKT38 cells have a stronger killing effect on tumor cell lines expressing CD1d and presenting endogenous lipid antigens, and prompt that the iNKT-TCR transfected NKT38 cells have a specific killing effect on tumors.

The invention relates to immunotherapy, and to invariant natural killer T (iNKT) cells, and iNKT cell immunotherapy. The invention concerns CAR-iNKT cell immunotherapy, in particular, mono- and bi-specific CAR-iNKT cell immunotherapy, as well as pharmaceutical compositions comprising these iNKT cells, and to their use in therapy, as well as therapies and methods for treating, preventing, or ameliorating cancer or infection. The invention also concerns the treatment of various leukaemias, such as acute lymphoblastic leukaemia (ALL), including infant ALL.

The present invention relates to chimeric antigen receptors (CAR) themselves, CAR constructs and T cell receptor (TCR) beta chain variable region beta (TCRV beta) CAR. The present invention relates to the use of CARs in immunotherapy, for example in the treatment, prevention or amelioration of cancer, for example T cell malignancies, as well as diseases caused or involved by pathogenic T cells, for example autoimmune diseases. In particular, the present invention relates to conventional T cells and constant natural killer T (iNKT) cells expressing anti-TCRV [beta] CAR and methods for their preparation. The present invention relates to nucleic acids and vectors encoding anti-TCRV [beta] CAR, pharmaceutical compositions comprising the constructs and cells, and medical uses of the compositions, anti-TCRV [beta] CAR constructs, and T cells and iNKT cells expressing anti-TCRV [beta] CAR.

Provided are chimeric ILT receptors (CIRs) that include a targeting region from ILT2 or ILT4, a transmembrane domain, and an intracellular domain (ICD). The ICD includes a signaling region (e.g., CD3 zeta (CD3ζ)) and optionally a costimulatory region (e.g., CD28, 4-1BB, OX40, and the like). Also provided are nucleic acids (e.g., expression vectors) encoding a subject CIR, and genetically modified cells (e.g., immune cells such as NK cells, T cells, iNKT cells, macrophages, and the like) expressing a subject CIR. For example, provided are genetically modified immune cells such as NK cells that include a nucleic acid encoding an ILT2 or ILT4 CIR. The subject CIRs are designed to activate cytotoxicity by immune cells such as NK cells, T cells, iNKT cells and macrophages against HLA-G expressing cancers.

The present disclosure is based at least in part on the discovery of novel BCMA antibodies or antigen-binding fragments thereof, and generally, genetically modified cells (e.g., iNKT cells, CAR T cells, etc.) expressing chimeric antigen receptors comprising anti-BCMA antibodies or antigen-binding fragments thereof exhibit improved properties, including increased binding to BCMA, killing of BCMA-expressing cancer cells in vitro and in vivo, and enhanced persistence in treated subjects.