82 results about "CD80" patented technology

The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to human B7-H4 (and optionally cynomolgus monkey, mouse, and / or rat B7-H4) and compositions comprising such antibodies or antigen-binding fragments thereof. In a specific aspect, the antibodies or antigen-binding fragments thereof that specifically bind to human B7-H4 increase T cell proliferation, increase interferon-gamma production, and / or deplete B7-H4 expressing cells via ADCC activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody or antigen-binding fragment thereof that specifically binds to human B7-H4.

Provided is a fusion protein comprising IL-2 protein and CD80 protein. A fusion protein containing CD80 fragment, immunoglobulin Fc, and an IL-2 variant can activate immune cells, such as natural killer cells, and at the same time, can control immune cell regulatory activity of regulatory T cells. Therefore, a pharmaceutical composition containing the fusion protein as an active ingredient is very industrially useful in that such pharmaceutical composition can increase immune activity in the body, and thus can be effectively used against infectious diseases as well as cancer.

A pharmaceutical composition for enhancing radiation therapy, containing a fusion protein dimer is disclosed. The fusion protein dimer includes an IL-2 protein and a CD80 protein. A method of radiation therapy for cancer, using the composition is also disclosed. The composition for enhancing radiation therapy may increase the effect of radiation therapy in cancer treatment.

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 present invention relates to: a fusion protein comprising an IL-2 protein and a CD80 protein; and a pharmaceutical composition for preventing or treating a cancer comprising chimeric antigen receptor (CAR)-expressing immune cells. When the fusion protein of the present invention is co-administered with the CAR-expressing immune cells, specifically CAR-T cells, immune activity of the CAR-T cells in tumors is enhanced and sustained. Moreover, when the fusion protein of the present invention is administered alone to a subject with recurrent cancer after the CAR-T cells have been administered, reactivation of the administered CAR-T cells may be induced to kill the recurrent cancer cells. Even when cancer cells are re-transplanted in an animal model in which cancer cells have been completely killed by co-administering the CAR-T cells and the fusion protein of the present invention, the immune activity of the CAR-T cells may be maintained for a long period of time by the fusion protein of the present invention, thereby continuously inhibiting the proliferation of the re-transplanted cancer cells. Accordingly, the fusion protein of the present invention not only enhances and prolongs the immune anticancer activity of the CAR-T cells, but also repeatedly reactivates the administered CAR-T cells, thereby maximizing the efficiency of the CAR-T cells as therapeutic cell resources to ultimately significantly improve the survival rate of patients.

The invention belongs to the field of biological medicine, and discloses a membrane binding type IL7 fusion protein, an engineered immune cell for expressing the membrane binding type IL7 fusion protein and application of the membrane binding type IL7 fusion protein. The fusion protein comprises an IL7 region and a transmembrane domain and can be expressed on a cell membrane, the tumor cell killing ability and the T cell survival ability of T cells expressing the fusion protein are both enhanced, and the aims of improving the tumor immune cell treatment effect and reducing the toxic and side effects are achieved. Particularly, the IL7 fusion protein anchors and expresses IL7 on the surface of a cell through transmembrane domains such as CD80 or PD-L1 and the like, so that (1) immune cells can be accurately regulated and controlled, the possibility that an excessive IL7 signal possibly causes autoimmune response or aggravates CRS is reduced, and the safety of the IL7 to immune cells such as T cells and the like is enhanced; (2) the half-life period of IL7 is prolonged, and the anti-tumor effect of adoptive immune cells is enhanced; and (3) the transmembrane fragment is linked with the IL7 through a hinge region of the flexible linker G4S, CD80 or PD-L1, so that the flexibility of the IL7 is enhanced, and the proliferation and killing functions of the IL7 on T cells are enhanced.

The present invention relates to the field of biomedicine, and more specifically, to a humanized anti-human PD-L1 antibody or antigen-binding fragment thereof and its use. The antibody or antigen-binding fragment thereof of the present invention has high affinity and strong binding specificity for PD-L1, effectively blocks the binding of PD-L1 to PD-1 and CD80, stimulates cytokine production, and exhibits significant anti-tumor effects. It can be used alone or in combination with other agents to prevent or treat immune disorders or tumor-related diseases.

Provided are immunomodulatory proteins containing an engineered variant CD80 extracellular domain that exhibits improved PD-L1 binding. The immunomodulatory proteins include variant CD80 domains with amino acid substitutions in the IgV domain. Among the provided immunomodulatory proteins are variant CD80-Fc fusion proteins. Also provided are cell therapies, such as T cell therapies, engineered with secretable or transmembrane immunomodulatory proteins containing the variant CD80 disclosed herein. In some aspects, the provided immunomodulatory proteins are capable of antagonizing PD-1 / PD-L1 in addition to providing CD28 costimulation in a PD-L1-dependent fashion. Also provided are nucleic acid molecules encoding the immunomodulatory proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological diseases, disorders, or conditions, such as cancer. Also provided are compositions and methods for making and using such immunomodulatory proteins as well as compositions and methods for making and using such cell therapies.

Provided is an anti-PD-L1 antigen binding protein, capable of binding to primate-derived PD-L1 with a KD value of 1×10−8 M or less. The antigen binding protein can block the binding of PD-1 and CD80 to PD-L1, stimulate the secretion of cytokines in immune cells, and can inhibit tumor growth and / or tumor cell proliferation. Also provided is a fusion protein, comprising human TGFBRII or a fragment thereof and the antigen binding protein. Also provided is an application of the antigen binding protein and / or the fusion protein in the prevention and treatment of tumors or cancers.

The invention provides a human FGFR3 (Fibroblast Growth Factor Receptor 3) antigen expression recombinant yeast vaccine as well as a construction method and application thereof. A specific primer is designed to amplify an FGFR3 gene, a pEGKT316-FGFR3 recombinant plasmid is constructed, a saccharomyces cerevisiae YEF473A strain is transformed, and the vaccine is prepared through induced expression and thermal inactivation. The vaccine can effectively activate DC cell maturation (CD80 + cell proportion reaches 78.7%) and promote Th1 type cell factor secretion (IL-12p70 reaches 5889pg / mL), and shows a remarkable tumor inhibition effect (plt; 0.05), and a novel specific treatment means is provided for postoperative immunotherapy of bladder cancer.

The present invention relates to antigen-binding proteins, related fragments thereof, for binding to CD80, and their use for treating various conditions such as inflammation and autoimmunity.

The invention discloses a novel immune enhancement system, which comprises a specific TLR4 agonistic polypeptide and a CD40 single-domain antibody. According to the polypeptide, a KLAKLAK core module is adopted, penetrating peptide and hydrophobic groups are modified, and an NF-kappa B / MAPK pathway can be effectively activated; the antibody is obtained through shark immune screening and has high affinity to CD40. When in combined application, the GM-CSF / IL-4-containing medium synergistically promotes the maturation of dendritic cells, so that the expression of CD80 / CD86 / MHC-II is improved by more than 2 times, the secretion amount of IL-12 reaches 165 pg / mL, and the proliferation rate of T cells is improved to 48.6%. Animal experiments show that the T cell stimulation index of a combined group reaches 6.2, and the serum IFN-gamma level is improved by 9 times. The composition provided by the invention can significantly enhance the DC vaccine efficacy, and has important application value in the field of tumor immunotherapy.

To provide an allogeneic tumor cell vaccine.SOLUTION: Provided is an allogeneic tumor cell vaccine, comprising: (1) a population of proliferation-incompetent, live, genetically engineered tumor cells expressing one or more tumor-specific antigens, the population comprising at least three stably expressed immunomodulatory molecules, at least three immunomodulatory molecules being OX40 ligand (OX40L), CD27 ligand (CD70), and CD28 ligand (CD28L) including CD80, CD86, or both, to induce one or more subpopulations of PBMCs to proliferate in response to the expressed immunomodulatory molecules and subsequently enter an effector phase to kill tumor cells, and the subpopulations of PBMC cells comprising one or more of T lymphocytes, natural killer (NK) cells, dendritic cells (DCs), or B lymphocytes; and (2) a pharmaceutically acceptable carrier.SELECTED DRAWING: None

The present invention provides a novel peptide, usages thereof and pharmaceutical composition having the same. The novel peptide is a first peptide. The pharmaceutical composition comprises the novel peptide and drug carriers, each novel peptide is connected to the surface of the drug carrier by a linker. The amino acid sequence of the first peptide is shown in SEQ ID NO: 1. The first peptide can bind to CD80 protein, besides, the present invention proves that the novel peptide of the present invention achieves the efficiency of enhancing cell uptake.

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.

The invention relates to the field of biological medicine, in particular to a lipidosome hybridized nano-vesicle vaccine loaded with piperazosin, a preparation method of the lipidosome hybridized nano-vesicle vaccine and application of the lipidosome hybridized nano-vesicle vaccine in preparation of anti-tumor drugs. The lipidosome hybrid nano-vesicle vaccine loaded with the prazosin, disclosed by the invention, can be used for inhibiting autophagy and inducing the death of immunogenic cells of tumors. The pirazosin-loaded liposome hybrid nano-vesicle vaccine can activate and promote the maturation of bone marrow-derived dendritic cells, the expression of costimulatory factors CD80 and CD86 is obviously increased, and the antigen presentation is better promoted. The lipidosome hybrid nano-vesicle vaccine loaded with the prazosin can promote infiltration of mature dendritic cells and T cells in tumor tissues, can remarkably inhibit tumor growth, can remodel a tumor microenvironment as a tumor vaccine, and effectively improves the immunotherapy effect.

In accordance with the present disclosure, macrocyclic compounds have been discovered that bind to PD-L1 and are capable of inhibiting the interaction of PD-L1 with PD-1 and CD80. These macrocyclic compounds exhibit in vitro immunomodulatory efficacy thus making them therapeutic candidates for the treatment of various diseases including cancer and infectious diseases.

The invention relates to the technical field of cellular immunotherapy, in particular to application of drafenib mesylate in preparation of a dendritic cell (DCs) immunologic adjuvant. The invention provides an application of drafenib mesylate in preparation of a dendritic cell immunologic adjuvant. It is found that darfenib mesylate can promote the maturation and migration functions of DCs, and the migration ability of DCs is remarkably improved. The DCs activation aspect of the darfenib mesylate comprises improvement of expression of maturation indexes CD80, CD40 and CD86 and expression of a migration index CCR7. Darrafenib mesylate used in the invention is a chemotherapeutic drug approved by FDA for clinical treatment of patients with BRAF V600 mutation positive non-resectable or metastatic melanoma, the application of Darrafenib mesylate in immunotherapy is discovered, new use of old drugs is realized, and the Darrafenib mesylate has significant economic value.

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).

An anticancer agent is provided comprising, as active ingredients, NK cells and a fusion protein comprising an IL-2 protein and a CD80 protein. In one specific formulation, a fusion protein comprising a CD80 fragment, an immunoglobulin Fc region, and an IL-2 variant can activate immune cells such as natural killer cells. Furthermore, since the pharmaceutical composition can effectively inhibit cancer, when co-administered with natural killer cells, it increases immune activity in the body, making it effective for cancer treatment and thus highly applicable to industry.

The invention relates to: a composition for culturing natural killer cells, comprising, as an active ingredient, a fusion protein comprising an IL-2 protein and a CD80 protein; and a method for preparing natural killer cells by using same. Particularly, a composition for culturing natural killer cells, comprising, as an active ingredient, a fusion protein comprising IL-2 or a variant thereof and CD80 or a fragment thereof, of the present invention; promotes the proliferation of natural killer cells, induces the expression of CD16 and NKp46, and increases the expression and secretion of granzyme B and perforin, thereby being effectively usable in the preparation of natural killer cells having an excellent anticancer immune function.

The invention discloses a polypeptide with tumor cell killing activity. The specific molecular target or the fusion polypeptide thereof is co-cultured with autoimmune cells of a subject, and then the autoimmune cells are transfused back into the body of the subject, so that targeted killing of tumor cells is realized, and the purpose of treating tumors is achieved. The dendritic cell (DC) load positive rate activated by the molecular target is greater than 90%. Furthermore, the activated DC cells highly express CD80 and CD86 on the surface, and can effectively present tumor antigens to T lymphocytes, thereby inducing to generate CTL cells with the capability of specifically recognizing cancer cells.

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 belongs to the technical field of biological medicines, and particularly relates to application of crizotinib in induction of tolerant dendritic cells (tDCs). The invention provides an application of crizotinib in induction of tolerant dendritic cells. It is found that crizotinib can serve as an efficient inducer of tDCs, the activation state of DCs can be remarkably inhibited, the maturation function of DCs can be inhibited, the immune stimulation capacity of DCs can be reduced, then activation of T cells is inhibited, and therefore the crizotinib plays a role in treating immune diseases such as GVHD. In the invention, the inhibition of crizotinib on DCs comprises reduction of expression of maturation indexes CD80, CD40 and CD86. The crizotinib used in the invention is an ALK / ROS1 inhibitor approved by FDA and is mainly used for treating non-small cell lung cancer, the application of the crizotinib in immunotherapy is found, new use of old medicines is realized, and the crizotinib has great economic value.

In accordance with the present disclosure, compounds have been discovered that bind to PD-L1 and are capable of inhibiting the interaction of PD-L1 with PD-1 and CD80. These macrocyclic compounds exhibit in vitro immunomodulatory efficacy thus making them therapeutic candidates for the treatment of various diseases including cancer and infectious diseases.

Various cells, stem cells, and stem cell components, including associated methods of generating and using such cells are provided. In one aspect, for example, an isolated cell that is capable of self-renewal and culture expansion and is obtained from a subepithelial layer of a mammalian umbilical cord tissue. Such an isolated cell expresses at least three cell markers selected from CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, or CD105, and does not express at least three cell markers selected from CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, or HLA-DR.