111 results about "Costimulatory Molecule" patented technology

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

The preparation method comprises the following steps: selecting PLGA (poly (lactic-co-glycolic acid)) with biocompatibility and biodegradability as a carrier material, loading an immunopotentiator alpha-tocopherol on PLGA nano-particles, and preparing the nano-particle immunologic adjuvant by using a nano-precipitation method, so as to obtain the nano-particle immunologic adjuvant with an immune synergistic effect. By controlling the polymer concentration and the drug concentration in the preparation process, the average particle size of the drug-loaded nano-particles is 90-120nm, the monodispersion coefficient is less than 0.2, the particle size of the product is uniform and stable, the encapsulation efficiency reaches 80% or more, the content of alpha-tocopherol in the nano-particles is 1-30%, and the drug-loaded nano-particles have a sustained-release effect of one month or more. The PLGA nanoparticles loaded with alpha-tocopherol can promote proliferation of mouse macrophages and enhance secretion of cell inflammatory cytokines and expression of surface costimulatory molecules, have a synergistic enhancement effect of the PLGA nanoparticles and alpha-tocopherol, and can be used as an effective immunologic adjuvant.

The invention relates to an application of a macrophage expressing an anti-uPAR chimeric antigen receptor in preparation of an anti-aging drug, and discloses a new application of the macrophage (CAR-M) expressing the anti-uPAR chimeric antigen receptor in senescence diseases, and the mechanism is that uPAR positive cells are specifically recognized and apoptosis of the uPAR positive cells is induced by targeting senescence cell surface antigen uPAR. According to the uPAR-CAR-M, a humanized anti-uPAR single-chain antibody is used as a chimeric antigen receptor recognition region, so that the chimeric antigen receptor has high specificity, and the chimeric antigen receptor is used for promoting the functions of macrophages by using a CD8 alpha transmembrane structural domain, a CD28 costimulatory molecule and a Megf10 sequence, so that a better killing effect is given to the CAR-M. The problems of inflammatory microenvironment caused by abnormal aggregation of senescence cells, chronic tissue damage and senescence-related disease treatment disorder are solved, and the application value for treating senescence-related diseases (such as osteoarthritis and the like) expressing uPAR is important.

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).

To provide a device, system, and method for neuromodulation of nerves adjacent to the splenic artery, specifically for stimulating neural activity in the nerves.SOLUTION: A system 50 for stimulating neural activity of the splenic artery nerves includes: at least one electrode 11, 12 for making signal-transmitting contact with the nerves at a site where the splenic artery does not directly contact the pancreas; and at least one controller 60 electrically coupled to the at least one electrode and configured to control the operation of the at least one electrode to apply electrical signals to the nerves. The electrical signals result in improvements in physiological parameters in a subject, and include one or more from the group consisting of a reduction in inflammatory cytokines, an increase in anti-inflammatory cytokines, an increase in catecholamines, changes in immune cell populations, changes in immune cell surface co-stimulatory molecules, a reduction in factors involved in inflammatory cascades, changes in levels of immune response mediators, and a reduction in splenic blood flow.SELECTED DRAWING: Figure 1

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 present invention is located in the field of immunotherapy. More specifically, the present invention relates to a composition of one or more nucleic acid molecules encoding functional immunostimulatory proteins such as IL-21, encoding co-stimulatory molecules, optionally in combination with cytokines and / or chemokines, to enhance the host immune response against tumor cells present in the body. The present invention further relates to a nucleic acid-containing composition or pharmaceutical formulation for use in the treatment of patients suffering from tumors and / or cancer diseases.

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 discloses application of lipopolysaccharide in preparation of a product for inducing phenotype transformation of neutrophil or treating tumors, the lipopolysaccharide can induce the neutrophil to improve surface anti-tumor markers, reduce surface tumor-promoting markers and promote expression of costimulatory molecules and MHC molecules, so that the neutrophil phenotype transformation can be induced, and the neutrophil phenotype transformation can be treated. Therefore, the neutrophil is promoted to be converted into the neutrophil with anti-tumor immunophenotype and the antigen presenting cell-like neutrophil, the immune system of an organism is activated, tumor cells are directly or indirectly killed, tumor growth and metastasis are inhibited, the lifetime of tumor-bearing mice is prolonged, and tumors can be thoroughly cured; in addition, the lipopolysaccharide can induce local inflammation of tumors, and then guide and drive aggregation and accumulation of neutrophils and activate the cytotoxic function of the neutrophils, so that the purpose of treating large-volume tumors is achieved.

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.

The invention relates to a method for detecting an immune state in thymus hyperplasia tissue in an EB (Epstein-Barr) virus infection state, which comprises the following steps of: constructing a kit comprising a quantum dot coupled CD19 antibody and a quantum dot coupled CD86 antibody; after the conjugate of the quantum dot and the specific antibody is specifically combined with an antigen on a B cell in a tissue slice sample, marking of the quantum dot on a costimulatory molecule on the surface of the B cell is realized; and judging the immune state of the thymus hyperplasia tissue according to a marking result. The quantum dot coupling antibody can be directly combined with an antigen on a tissue slice to realize direct marking of the quantum dot coupling antibody on the tissue slice, so that the B cell surface costimulatory molecules in a thymus hyperplasia tissue microenvironment are quantified and positioned, the relationship between the B cell surface costimulatory molecules and thymus hyperplasia-related autoimmune diseases is determined, and the accuracy and the sensitivity of the B cell surface costimulatory molecules in the thymus hyperplasia tissue microenvironment are improved. The immune state of the thymus hyperplasia tissue microenvironment can be evaluated, and autoimmune diseases can be predicted.

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.