47 results about "Costimulatory Molecule" patented technology

The invention discloses a method and a device for detecting CAR (Chimeric Antigen Receptor) cells. The method comprises the following steps: taking a genome of a sample to be detected as a template, carrying out fluorescent quantitative PCR reaction by using a primer and a probe aiming at the sequence of a CD8 alpha transmembrane region-41 BB costimulatory molecule in a CAR gene to obtain a CT value, and calculating the copy number of the CAR gene according to the CT value and a standard curve to obtain the CAR cell distribution. Specific primers and probes are designed for CAR cells containing CD8 alpha transmembrane region-41BB costimulatory molecules, a fluorescent quantitative PCR method for detecting the copy number of CAR genes is developed, then the CAR cells are quantified, and it is proved that the method has wide applicability through multi-angle verification analysis and limitation of detection standards.

The application provides a factor composition for activating DC cells and a method for application thereof, and belongs to the technical field of cell preparations.The factor composition for activating DC cells provided by the application comprises the following components: rhGM-CSF, rhIL-4, rhSCF, rhTNF-alpha, IFN-alpha, insulin and lycium barbarum polysaccharide.Through the synergistic effect between the components, the application can not only promote the differentiation of PBMC into DC cells, increase the proportion of DC cells, increase the initial amount of DC cells, promote the proliferation of DC cells, increase the activity of DC cells, but also can increase the expression of antigen costimulatory molecules and reduce the culture cycle of DC cells.

The present application relates to a kind of universal preparation method for presenting tumor antigen and highly activated T cell exosome, belong to biomedical and immunotherapy technical field.The present application described method is first synthesized the tumor antigen specificity nano stimulant capable of activating dendritic cell, makes dendritic cell carry IFN-β, expresses specific tumor-related antigen and costimulatory molecule, to solve the problems, such as low antigen presentation efficiency, T cell activation deficiency and high cost of individualized treatment in the existing tumor immunotherapy method.Exosome is extracted from the supernatant of the above dendritic cell culture.The preparation method of the present application not only significantly improves the efficiency of exosome as antigen presentation carrier, effectively and specifically stimulates T cell, but also reduces the preparation cost, provides more effective general solution for tumor immunotherapy, has wide application prospect and clinical value.

The invention belongs to the technical field of vaccines, and particularly relates to a manganese-based platelet carrier vaccine based on a biomimetic mineralization technology and application of the manganese-based platelet carrier vaccine in immunotherapy. A manganese-based shell is deposited on the surface of a platelet, immunocompetence molecules such as CD40L and PF4 are expressed on the surface of the platelet, dendritic cells (DC) can be activated by directly contacting or secreting cell factors, and antigen presentation is promoted; in addition, deposited manganese ions can activate a cGAS-STING pathway, and meanwhile, CD40 / CD80 / CD86 / MHC-II costimulatory molecular expression on the surface of the DC is up-regulated. The vaccine adjuvant provided by the invention can be used for loading an antigen to form a three-in-one vaccine complex of the antigen (loaded on a platelet membrane), the platelet and a manganese shell, so that not only is the natural targeting capability of the platelet retained, but also DC cross presentation is enhanced through continuous release of manganese ions, finally CD8 + T cells are synergistically activated to react with an antibody, and the immune response of the antigen is enhanced. The antiviral immune response of the body is enhanced.

Provided herein are novel anti-CD20x anti-CD28 antibodies and methods of using such antibodies to treat B cell malignancies. The subject anti-CD20x anti-CD28 antibodies are capable of agonically binding to a CD28 costimulatory molecule on a T cell and to CD20 on a tumor cell. Thus, such antibodies enhance anti-tumor activity at tumor sites. The subject antibodies provided herein are particularly useful in the treatment of B-cell malignancies in combination with other anti-cancer therapies (e.g., anti-CD3 x anti-CD20 x anti-CD79b antibodies).

This invention belongs to the field of biotechnology, specifically relating to a high-affinity anti-tumor NK cell, its preparation method, and its application. This invention designs NK92 cells transfected with a haPD1 high-affinity chimeric conversion receptor, wherein the high-affinity chimeric conversion receptor includes the extracellular segment of haPD-1, the transmembrane segment of CD28, the intracellular segment of DAP10, and the intracellular segment of CD3ζ. This invention prepares haChR3-NK92 cells through the construction of a recombinant lentiviral vector, lentiviral packaging, and lentiviral transfection of NK92 cells. In this invention, haPD-1 serves as the extracellular recognition domain of the CAR structure, specifically binding to PD-L1 on tumor cells to achieve a stronger tumor-killing effect. The co-stimulatory molecule CD28 serves as the transmembrane region to transmit extracellular information into the cell, integrating the adaptor protein DAP10 of the NK cell surface activator receptor NKG2D into the cell, and further embedding the intracellular segment CD3ζ commonly used in CAR design to jointly promote NK cell activation. The preparation method of this invention can successfully construct haChR3-NK92 cells, achieve the expression of the target plasmid, and be applied in anti-tumor drug research.

The present disclosure provides a population of genetically modified immune cells and uses thereof, the modified immune cells comprising (i) a chimeric antigen receptor (CAR) targeting a target protein on a target cell; (ii) a first immunomodulatory fusion protein comprising an ectodomain derived from a protein of tumor necrosis factor (TNF) superfamily, and an endodomain derived from a costimulatory molecule of a TNF receptor superfamily protein; (iii) a second immunomodulatory fusion protein comprising an ectodomain derived from a protein of TNF receptor superfamily, and an endodomain derived from a common g-chain cytokine receptor; and (iv) a third immunomodulatory fusion protein comprising an ectodomain derived from the same TNF receptor superfamily protein as in the second immunomodulatory fusion protein, and an endodomain derived from an a or b receptor subunit of the common g-chain cytokine receptor family.

Provided herein are novel anti-CD28x anti-ENPP3 antibodies and methods of using such antibodies to treat ENPP3 related cancers. The subject anti-CD28x anti-ENPP3 antibodies are capable of agonically binding to a CD28 costimulatory molecule on a T cell and to ENPP3 on a tumor cell. Thus, such antibodies selectively enhance anti-tumor activity at the tumor site while minimizing peripheral toxicity. The subject antibodies provided herein may particularly be used in combination with other anti-cancer therapies, including, for example, bispecific antibodies for the treatment of ENPP3-associated cancers.

The application discloses an antigen-engineered nanovesicle vaccine (AN-FV) and a preparation method and application thereof. The vaccine is formed by fusion of vesicles of tumor cell membranes obtained by pretreatment of functionalized nanometer preparations and vesicles of mature dendritic cell membranes; the functionalized nanometer preparations contain autophagy inhibiting siRNA and an immunogenicity enhancer, and can synergistically improve MHC-I expression of tumor cells and antigen immunogenicity. The vaccine of the application simultaneously presents high-density MHC-I-antigen peptide complexes and CD80 / CD86 costimulatory molecules on the surface of a single particle, simulates an immune synapse in a nanometer scale, and thus efficiently activates tumor-specific T cells. The vaccine integrates antigen source engineering, physiologicalization of costimulatory signals and nanometer platform integration, and provides a new scheme for overcoming the treatment bottleneck of immune "cold" tumors such as pancreatic cancer.

The invention provides trispecific antibodies having one binding site binding to a target antigen on a cancer cell, pathogen, infected cell or autoreactive cell, and second and third binding sites binding to CD3 and CD28 respectively. Such antibodies can crosslink CD3 and CD28 on the surface of T cells at the cell-to-cell junction with target cells, and trigger CD3-mediated signal transduction (Signal 1) and costimulatory molecule-mediated signal transduction (Signal 2) for activation of T cells resulting in efficient elimination of target cells.

Provided herein are particles containing a fusion molecule comprising an adhesion molecule linked to a costimulatory molecule or an activation molecule, as well as vectors such as lentiviral vectors containing the same, cells containing the same, and methods for using the same. The particle may be a lentiviral particle that displays a fusion molecule containing a) the CD58 extracellular domain or a functional fragment thereof, b) an antigen-binding fragment of an anti-CD3 antibody, and c) the CD80 or CD86 extracellular domain or a functional fragment thereof, and a viral glycoprotein (G protein) on the surface of the particle.

Described herein are methods and compositions for regulatory T cells (Tregs) that are modified to express a chimeric antigen receptor (CAR) that targets OX40L. Aspects of the invention relate to administering these modified Tregs to a subject having an inflammatory or autoimmune condition.

CD38 is expressed on malignant plasma cells. CD28 is a costimulatory molecule required for T-cell activation and survival. Provided herein are novel anti-CD38 antibodies, anti-CD28 antibodies, and bispecific antibodies (bsAbs) that bind to both CD38 and CD28 and act as costimulatory agents to activate T cells via binding CD80 and / or CD86. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing CD38. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced CD38-targeted immune response is desired and / or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of various cancers, including multiple myeloma, lymphoma, and leukemia.

In some embodiments, compositions and methods relating to isolated artificial antigen presenting cells (aAPCs) are disclosed, including aAPCs comprising a U937 cell modified to express one or more co-stimulatory molecules including CD64, CD86, 4-1BBL and / or OX40L. Further provided are lipid nanoparticles (LNPs) conjugated to one or more co-stimulatory molecules including CD64, CD86, 4-1BBL and / or OX40L. In some embodiments, methods of expanding tumor infiltrating lymphocytes (TILs) with aAPCs or LNPs and methods of treating cancers using TILs after expansion with aAPCs or LNPs are also disclosed.

The present disclosure relates generally to binding proteins comprising an antigen binding site, a T cell receptor binding site, and a T cell costimulatory molecule binding site. The disclosure also relates to pharmaceutical compositions comprising such binding proteins, nucleic acid molecules encoding such binding proteins and vectors comprising such nucleic acid molecules. The disclosure also relates to methods of treating a disorder or condition using such binding proteins and pharmaceutical compositions, binding proteins and pharmaceutical compositions for use in the treatment of a disorder or condition, and the use of such binding proteins and pharmaceutical compositions for the manufacture of a medicament for the treatment of a disorder or condition.

A dual-targeting chimeric antigen receptor (CAR) and its encoding gene, a recombinant expression vector, natural killer cells, and applications thereof are provided, relating to the field of tumor immunotherapy. The dual-targeting CAR includes a dual-CAR molecular encoding sequence sequentially connected encoding sequences of: an extracellular antigen-binding region, a transmembrane region, and an intracellular signal transduction region. PD1 molecule extracellular domain and NKG2D molecule extracellular domain serve as a first recognition target and a second recognition target respectively. When the PD1 molecule extracellular domain recognizes PD-L1 molecules on tumor cells, the negative regulatory signal is transmitted downward, triggering activation of the DAP10 activating receptor pathway and converting it into a positive activation signal. Simultaneously, when the NKG2D molecule extracellular domain recognizes NKG2DL molecules on tumor cells, NK cell activation is induced. Under the synergistic action of costimulatory molecules 4-1BB and CD3ζ, the anti-tumor therapeutic efficacy of NK cells is significantly enhanced.

The application discloses a PGPC / CpG combined adjuvant and a method and application thereof for improving the efficiency of a type I dendritic cell anti-tumor vaccine, and belongs to the technical field of biotechnology. The method for improving the efficiency of the type I dendritic cell anti-tumor vaccine by using the PGPC / CpG combined adjuvant disclosed by the application stimulates cDC1 by using the PGPC / CpG combined adjuvant; the final concentration of the CpG is 1 mM, and the final concentration of the PGPC is 25 µg / mL. The PGPC / CpG combined adjuvant can significantly promote the expression of the co-stimulating molecules CD40, CD80, CD86 on the surface of cDC1, and inflammatory factors IL-12, TNFɑ and IL-1β, enhance the ability of the cDC1 to induce CD8 + T cell activation, proliferation and differentiation into anti-tumor effector T cells, and effectively improve the in-vivo anti-tumor effect of the cDC1 vaccine.

This invention provides a method for preparing a composition of manipulated cells. [Solution] The method includes (a) a step of incubating an input composition containing CD4+ primary human T cells enriched T cells under stimulating conditions including (i) a stimulating reagent capable of activating one or more intracellular signaling domains of one or more components of a TCR complex and / or one or more intracellular signaling domains of one or more co-stimulatory molecules, and (ii) the presence of one or more cytokines, at least one of which is recombinant human IL-2 or contains recombinant human IL-2, thereby generating a stimulated composition; and (b) a step of introducing a recombinant receptor into the stimulated composition, thereby generating an engineered composition containing engineered T cells.

In some embodiments, compositions and methods relating to isolated artificial antigen presenting cells (aAPCs) are disclosed, including aAPCs comprising a U937 cell modified to express one or more co-stimulatory molecules including CD64, CD86, 4-1BBL and / or OX40L. Further provided are lipid nanoparticles (LNPs) conjugated to one or more co-stimulatory molecules including CD64, CD86, 4-1BBL and / or OX40L. In some embodiments, methods of expanding tumor infiltrating lymphocytes (TILs) with aAPCs or LNPs and methods of treating cancers using TILs after expansion with aAPCs or LNPs are also disclosed.

Provided herein are particles comprising a fusion molecule comprising an adhesion molecule linked to a costimulatory molecule or an activation molecule, as well as vectors, such as lentiviral vectors, comprising the same, cells comprising the same, and methods of using the same. The particle may be a lentiviral particle that displays on the surface of the particle a fusion molecule comprising: a) a CD58 extracellular domain, or a functional fragment thereof, b) an antigen-binding fragment of an anti-CD3 antibody, and c) a CD80 or CD86 extracellular domain, or a functional fragment thereof, and a viral glycoprotein (G protein).

The invention discloses application of kinsenoside in preparation of drugs for inhibiting metabolic inflammation and improving obesity, kinsenoside regulates and controls an immune system, induces dendritic cells to express immunosuppressive molecules PD-L1 and inhibits costimulatory molecules CD86, so that tolerance of kinsenoside is maintained. The effect further inhibits the activation and infiltration of downstream T cells, and finally reduces the recruitment and activation of macrophages in fat and liver tissues, and breaks the vicious circle of metabolic inflammation. Animal experiments show that the kinsenoside can effectively inhibit weight gain induced by high fat diet and improve abnormal glucose tolerance, insulin resistance, liver lipid deposition and dyslipidemia. The invention discloses the effect of kinsenoside in treating obesity and related complications thereof through a targeted immune metabolic axis for the first time, and provides a new strategy and a candidate compound for developing novel and safe anti-obesity drugs.

Fusion proteins comprising a T cell targeting element and a co-stimulatory molecule and combinations thereof are provided. VSVG virus glycoprotein variants are provided. Also provided is a recombinant virus particle comprising the fusion protein and a VSVG variant. Further provided are uses of the recombinant viral particles for in vivo immune cell therapy.

Provided herein are novel anti-CD28 x anti-PSMA antibodies and methods of using such antibodies for the treatment of PSMA-associated cancers. Subject anti-CD28 x anti-PSMA antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and PSMA on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful in combination with other anti-cancer therapies (e.g., anti-CD3 x anti-PSMA antibodies) for the treatment of prostate cancers.

The invention provides trispecific antibodies having one binding site binding to a target antigen on a cancer cell, pathogen, infected cell or autoreactive cell, and second and third binding sites binding to CD3 and CD28 respectively. Such antibodies can crosslink CD3 and CD28 on the surface of T cells at the cell-to-cell junction with target cells, and trigger CD3-mediated signal transduction (Signal 1) and costimulatory molecule-mediated signal transduction (Signal 2) for activation of T cells resulting in efficient elimination of target cells.

@biotinThe invention discloses a preparation method and application of a lipid bispecific antibody nanosheet capable of activating a cGAS-STING pathway to enhance anti-tumor immune response of cDC1 and PD-1 + T cells in the field of biological medicine, and the preparation method comprises the following steps: firstly, preparing an Mg0.2 Co0.8 (OH) 2 nanosheet, then wrapping the prepared Mg0.2 Co0.8 (OH) 2 nanosheet with liposome, then coupling biotin with a monoclonal antibody, and finally preparing the lipid bispecific antibody nanosheet capable of activating the cGAS-STING pathway to enhance the anti-tumor immune response of the cDC1 and PD-1 + T cells. Streptavidin is coupled with lipidosome of a nano cobalt magnesium tablet, LMC is finally fused with alphaCLEC9A (at) biotin and alphaPD-1 (at) biotin, Co < 2 + > and Mg < 2 + > released by MC enter cytoplasm, a cGAS-STING pathway is synergistically activated, DC is promoted to secrete IFN-1 and costimulatory molecules, and the antigen presentation capacity is enhanced; the bispecific antibody is combined with CLEC9A + cDC1 and PD-1 + T cells at the same time, promotes physical crosstalk of the CLEC9A + cDC1 and PD-1 + T cells in tumors and drainage lymph nodes, and activates CD8 + T cells to proliferate and differentiate into effector T cells; in a TC-1 tumor-bearing mouse, LMC-NBiE promotes CD8 + T cell infiltration and tumor cell apoptosis and inhibits tumor growth by inducing high expression of CLEC9A + cDC1 and cross presentation of tumor antigens.

The present disclosure provides multimeric T cell engaging binding molecules comprising five, four, or two bivalent binding units that bind to a target antigen and a modified J chain, wherein the modified J chain comprises a J chain or a functional fragment or variant thereof, an anti-CD3 antigen-binding domain, and a heterologous polypeptide comprising a polypeptide agonist of a T cell costimulatory molecule. The T cell costimulatory molecule can be, for example, CD28 or 4-1BB. The present disclosure further provides multimeric binding molecules comprising five, four, or two bivalent binding units that bind to a target antigen and a modified J chain, wherein the modified J chain comprises a J chain or a functional fragment or variant thereof and a 4-1BB ligand (4-1BBL) trimer that can engage with and activate 4-1BB on a target cell.

To provide a pharmaceutical composition for treating cancer. [Solution] The pharmaceutical composition comprises a hydrogel matrix containing a chimeric antigen receptor (CAR), an NK cell receptor, an NK T cell receptor, or a viral vector encoding a T cell receptor, wherein the hydrogel matrix is ​​formulated for administration to a target. Preferably, the pharmaceutical composition further comprises the hydrogel matrix containing one or more antibodies, cytokines, or costimulatory molecules that activate T cells, macrophages, natural killer (NK) cells, NK T cells, tumor-infiltrating NK cells (TINK), tumor-infiltrating lymphocytes (TIL), or medullary lymphocytes (MIL).

This specification provides novel anti-CD28 × anti-ENPP3 antibodies and methods for using such antibodies for the treatment of ENPP3-related cancers. The target anti-CD28 × anti-ENPP3 antibodies can agonist-conjugate CD28 costimulatory molecules on T cells and ENPP3 on tumor cells. Thus, such antibodies selectively enhance antitumor activity at tumor sites while minimizing peripheral toxicity. The target antibodies provided herein are particularly useful in combination with other anticancer therapies, for example, bispecific antibodies for the treatment of ENPP3-related cancers.

Provided herein are recombinant poxviruses comprising heterologous or native nucleic acids specifying excess double-stranded RNA (dsRNA) early in infection, which may further comprise heterologous nucleic acids encoding one or more costimulatory molecules, and / or heterologous nucleic acids encoding one or more infectious disease-associated antigens or tumor-associated antigens, as well as pharmaceutical compositions comprising such recombinant poxviruses and methods and uses thereof. The recombinant poxviruses provided herein enhance innate and adaptive immune activation in subjects compared to identical recombinant poxviruses lacking heterologous or native transcription units specifying excess early dsRNA.

The present invention refers immune cells expressing a TCR and a co-stimulatory. In particular, the invention refers to immune cells expressing a (i) T cell receptor (TCR) specific for a TCR specific for NY-ESO-1 peptide SLLMWITQC and (ii) a chimeric co-stimulatory receptor comprising an extracellular domain derived from PD-1 (CD279) and an intracellular domain derived from 4-1BB (CD137).