92 results about "Costimulatory Molecule" patented technology

The present application provides compositions and methods of use relating to modified immune effector cells for use in the treatment of diseases such as cancer. The modified immune effector cells disclosed herein can be engineered to exhibit decreased expression and or activity of immune adhesion / costimulatory molecules, MHC proteins, and / or T cell receptors. The modified immune effector cells can also comprise chimeric antigen receptors.

A method for generating or expanding a population of natural killer cells (NK cells) via using modified K562 feeder cells having expression of factors capable of increasing activation and proliferation of natural killer cells, wherein the factors capable of increasing activation and proliferation of NK cells include: (A) a co-stimulatory molecule comprises CD80 molecules, and 4-1BBL molecules; and (B) a cytokine, specifically membrane-bound IL-21 (mbIL-21).

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 invention discloses application of cucurbitacine I in preparation of cisplatin sensitization drugs for treating ovarian cancer, and belongs to the technical field of sensitization drugs for tumor chemotherapy. CuI and CDDP have a good synergistic tumor inhibition effect on ovarian cancer, CuI may directly act on EGFR and can be combined with CDDP to significantly inhibit phosphorylation of EGFR and downstream STAT3 protein thereof, induce DNA damage and ROS accumulation, amplify a pyroptosis effect, increase release of TAAs and DAMPs, promote DC maturation and promote infiltration of CD8 + T cells and memory T cells in TIME in vivo, so that the tumor inhibition effect on ovarian cancer is improved. The expression of an inhibitory costimulatory molecule PD-1 in CD8 + T cells is reduced, the whole body immune effect is activated, and the TIME of the ovarian cancer is remarkably improved. The combined treatment strategy of CuI-CDDP controls the progress of ovarian cancer from a dual mechanism of directly inhibiting tumor cells and promoting anti-tumor immune activation.

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 present invention provides a clinically applicable method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring radiotherapy or chemotherapy, and without development of GVHD or graft rejection. Aspects of the present invention are based on the discovery that the depletion of the endogenous stem cell niche facilitates efficient engraftment of stem cells into that niche. In particular, the present invention combines the use of selective ablation of endogenous stem cells with a combination of antibodies specific for CD117, and agents that modulate immunoregulatory signaling pathways, e.g. agonists of immune costimulatory molecules, in combination with the administration to the recipient of exogenous stem cells, resulting in efficient, long-term engraftment, even in immunocompetent recipients.

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.

Engineered, replication-deficient influenza viruses that are infectious and stimulate broadly-cross protective immunity against multiple different influenza strains have been developed. Compositions and methods for providing protective immune responses against influenza are provided. The methods deliver compositions of intact, replication-deficient influenza viruses by intradermal administration in an amount effective to elicit or stimulate a cross-protective immune response to influenza viruses in the recipient following a single administration. Because the engineered influenza viruses are non-replicating, they are safe and effective in immunocompromised subjects. Methods for delivering co-stimulatory molecules, growth factors, adjuvants and / or cytokines together with the non-replicating influenza viruses are also provided.

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).

Disclosed herein are immune cell engagers. The immune cell engager may include a cell binding domain, an immune cell adhesion molecule, an immune cell costimulatory molecule, or a combination thereof. Methods of use and production are further provided.

The invention discloses an anti-psoriasis tolerant dendritic cell as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The tolerant dendritic cell is obtained by in-vitro induction of an immunomodulator and is loaded with a psoriasis-related antigen; wherein the psoriasis related antigen is antibacterial peptide LL37, own nucleotide or a compound of the antibacterial peptide LL37 and the own nucleotide. The tolerable dendritic cell can inhibit type II expression of costimulatory molecules and main histocompatibility complexes and induce generation of regulatory T cells, so that the effects of treating psoriasis and effectively inhibiting relapse of psoriasis are achieved. Therefore, the tolerant dendritic cell provided by the invention has a good application prospect, and provides a brand new direction for treatment of psoriasis.

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.

Provided herein are particles comprising a fusion molecule comprising an adhesion molecule linked to a co-stimulatory molecule or an activating molecule; the present invention relates to fusion molecules, as well as vectors such as lentiviral vectors comprising the fusion molecules, cells comprising the fusion molecules, and methods of using the fusion molecules. The particle may be a lentiviral particle that displays a fusion molecule on a surface of the particle, the 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 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 description generally relates to binding proteins comprising antigen-binding sites, a T-cell receptor-binding site, and a T-cell costimulatory molecule-binding site. The description also relates to pharmaceutical compositions comprising such binding proteins, nucleic acid molecules encoding such binding proteins, and vectors comprising such nucleic acid molecules. The description further relates to methods for 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 to treat a disorder or condition.

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 a tumor-associated fibroblast targeting nano adjuvant as well as a preparation method and application thereof, and belongs to the field of nano drugs. The nano adjuvant (named as PF9PEI and alpha PC NPs) provided by the invention is coupled with PEI25K modified by 3-perfluorobutyl-1, 2-epoxypropane by utilizing a PD-L2 targeting peptide nrirgenyryh, so that an efficient gene vector (PF9PEI) is formed, and is used for loading an alpha PD-L1-P2A-CD86 plasmid. According to the nano adjuvant, CAFs can be reprogrammed into engineered antigen presentation CAFs by expressing a costimulatory molecule CD86, so that T cell immunity of breast cancer specificity is activated, and T cell failure is retarded at the same time. Besides, the engineered CAFs generated by the nano adjuvant generate alphaPD-L1 locally, so that the immune escape mechanism of breast cancer cells is effectively blocked, and the immune surveillance function of T cells is recovered. After radiotherapy, by using the nano adjuvant for treatment, the generation of central memory T cells is promoted, the progress of the same solid tumor is inhibited, the tumor metastasis is eliminated, and the tumor recurrence is inhibited.

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.

The present invention relates to a chimeric antigen receptor, a recombinant vector, a recombinant cell, and a preparation method and application thereof. The recombinant costimulatory molecule of the CAR includes a first module and a second module; the first module is a first N-terminal segment, and the second module is a connected second intermediate segment and a second C-terminal segment, or a connected second N-terminal segment, a second intermediate segment and a second C-terminal segment; or, the first module is a connected first N-terminal segment and a first intermediate segment, or a connected first N-terminal segment, a first intermediate segment and a first C-terminal segment, and the second module is a second C-terminal segment, a connected second intermediate segment and a second C-terminal segment, or a connected second N-terminal segment, a second intermediate segment and a second C-terminal segment; the two types of costimulatory domains are split into three parts from the N-terminus to the C-terminus to obtain the above-mentioned segments. The above-mentioned CAR can expand the functional space of CAR-T cell downstream signals.

The present invention discloses the application of atorvastatin calcium in the preparation of an anti-tumor preparation for enhancing dendritic cell vaccines, belonging to the technical field of immune adjuvants. The application of atorvastatin calcium disclosed by the present invention in the preparation of an anti-tumor preparation for enhancing dendritic cell vaccines. Atorvastatin calcium can be used in the preparation of dendritic cell vaccines, significantly up-regulating the expression of pro-inflammatory factors Tnfa, Il6, Il12p40, and Il12p35 and the expression of surface co-stimulatory molecules CD80 and CD86 in dendritic cells, promoting the ability of dendritic cells to mediate the activation of CD4+ T cells and CD8+ T cells and their differentiation into IFNγ-secreting effector cells, and effectively enhancing the anti-tumor effect of dendritic cell vaccines. The present invention provides a method for using atorvastatin calcium in the preparation of dendritic cell vaccines to promote the efficacy of dendritic cell vaccines, providing a new direction for tumor prevention and treatment.

Provided herein are novel anti-CD28×anti-PSMA antibodies and methods of using such antibodies for the treatment of PSMA-associated cancers. Subject anti-CD28×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×anti-PSMA antibodies) for the treatment of prostate cancers.

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.

Viral particles for activating and transducing immune cells in vitro or in vivo, as well as compositions and methods for using said viral particles are provided. The present disclosure is based, at least in part, on the discovery that viral particles can be produced such that a cell surface protein is expressed on the viral envelope to simultaneously prime and transduce immune cells. In particular, as demonstrated herein, viral particles expressing a TCR targeting molecule and a costimulatory molecule enhance cell activation in vivo and transduction of nucleotides encoding a polypeptide of interest as compared to viral particles expressing only the TCR targeting molecule.

The invention belongs to the technical field of biological medicine, and relates to a dendritic cell vaccine as well as a preparation method and application thereof, in particular to a dendritic cell vaccine based on enhancement of dendritic cell maturation and vaccine efficiency and application of the dendritic cell vaccine in tumor treatment. The dendritic cell disclosed by the invention is a dendritic cell with deletion of a metabotropic glutamate receptor 4 or a dendritic cell treated by forskolin, and the dendritic cell can promote the expression of co-stimulatory molecules on the surface of the dendritic cell; the proliferation of T cells is promoted; inducing the effector T cells to secrete interferon gamma and granzyme B; the killing capability of T cells on tumor cells is enhanced. The dendritic cell vaccine disclosed by the invention comprises dendritic cells loaded with antigens, wherein the antigens are liver cancer cell lysates. The dendritic cell vaccine disclosed by the invention has an anti-tumor effect and can be used for preparing anti-tumor medicines.

To provide a method for genetically engineering T cells for use in a cell therapy without cell expansion, as well as compositions of the generated T cells and uses thereof for treating a subject.SOLUTION: Disclosed is a method for producing a composition of engineered T cells, the method comprising the steps of: (a) exposing a composition comprising primary T cells to a stimulator under conditions to stimulate T cells thereby generating a stimulated population, where the stimulator activates one or more intracellular signaling domains of one or more components of TCR complex, and activates one or more intracellular signaling domains of one or more co-stimulatory molecules; (b) introducing to the T cells of the stimulated population a heterologous polynucleotide encoding a recombinant protein thereby generating a population of transformed cells; (c) incubating the population of transformed cells; and (d) following the incubation, harvesting T cells of the transformed cell population thereby producing a composition of the engineered cells.SELECTED DRAWING: Figure 13A

To provide a patient-specific modified T cell intended for treatment of cancer, methods for generating the modified T cell, and pharmaceutical compositions comprising the modified T cell.SOLUTION: The present invention provides a modified T cell comprising: a nucleic acid capable of downregulating expression of an endogenous gene selected from the group consisting of TCR α chain, TCR β chain, β-2 microglobulin, an HLA molecule, CTLA-4, PD1 and FAS; and a nucleic acid encoding a chimeric antigen receptor (CAR) comprising an antigen binding domain, a transmembrane domain and an intracellular domain of a co-stimulatory molecule. Also provided are methods for generating the modified T cell. Further provided are pharmaceutical compositions comprising the modified T cell for adoptive therapy and for treating a condition, such as an autoimmune disease.SELECTED DRAWING: Figure 1A

The present disclosure relates to a bifunctional fusion protein composed of IL-15 and an antibody against a T cell co-stimulatory molecule. The T cell co-stimulatory molecule is 4-1BB, ICOS or OX40, preferably 4-1BB; the fusion protein comprises: (1) an antibody against a T cell co-stimulatory molecule; (2) a conjugate of IL-15 and IL-15R Sushi domain linked by a second linker; and (3) a matrix metalloproteinase-cleavable first linker for linking the Fc region of the heavy chain of the antibody against the T cell co-stimulatory molecule to the conjugate of IL-15 and IL-15R Sushi domain.

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.