32 results about "CD80" patented technology

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.

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 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 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.

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 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.

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.

The present disclosure provides methods of treating PD-L1 negative tumors, the methods comprising administering fusion proteins comprising the extracellular domain of human cluster of differentiation 80 (CD80) and the fragment crystallizable (Fc) domain of human immunoglobulin G 1 (IgG1).

The application relates to the field of biological medicines, and discloses a tumor vaccine containing a polysaccharide adjuvant and application thereof. The tumor vaccine formula comprises, in terms of mass fractions, 100 parts of WT1-CM-betaG NPs, 10 parts of astragalus polysaccharide, 5 parts of quillaja saponin and 1 part of a TLR agonist. The WT1-CM-betaG NPs comprise, in terms of mass fractions, 10 parts of a WT1 polypeptide combination, 50 parts of carboxymethylated beta-glucan nanoparticles CM-betaG NPs, 10 parts of EDC and 6 parts of NHS. The WT1 polypeptide is covalently connected to the carboxymethylated beta-glucan nanoparticles through chemical coupling, and then cooperates with the adjuvant, has a synergistic effect on improving the ability of stimulating DC maturation (high expression of CD80 / CD86 / MHC-II) and improving the secretion of key Th1 type cytokine IL-12p70, can improve the antitumor effect, and has a wide application in treating WT1 positive tumors.

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.

This invention belongs to the field of biomedical technology, specifically relating to the application of crizotinib in inducing tolerant dendritic cells (tDCs). This invention provides the application of crizotinib in inducing tolerant dendritic cells. This invention discovers that crizotinib can act as a highly effective inducer of tDCs, significantly inhibiting the activated state of DCs, suppressing their maturation function, reducing their immunostimulatory capacity, and thus inhibiting T cell activation, thereby exerting a therapeutic effect in immune diseases such as GVHD. The inhibitory effects of crizotinib on DCs in this invention include reducing the expression of maturation markers CD80, CD40, and CD86. The crizotinib used in this invention is an FDA-approved ALK / ROS1 inhibitor, primarily used for the treatment of non-small cell lung cancer. This invention discovers its application in immunotherapy, realizing the repurposing of an existing drug, and has significant economic value.

This invention provides a method for screening peptides that specifically target T cells, comprising providing T cells having a subset selected from CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD16, CD25, CD26, CD27, CD28, CD30, CD38, CD39, CD40L, CD44, CD45, CD62L, CD69, CD73, CD80, CD83, CD86, CD95, CD103, CD119, CD126, CD150, CD152 (CTLA-4), CD153, CD154 (CD40L) The T cells are labeled with at least one of the following surface antigen markers: CD161, CD183, CD223, CD254, CD275, CD45RA, CXCR3, CXCR5, FasL, IL18R1, CTLA-4, OX40, GITR, LAG3, ICOS, PD-1, leu-12, TCR, TLR1, TLR2, TLR3, TLR4, TLR6, NKG2D, CCR, CCR1, CCR2, CCR4, CCR6, and CCR7. The T cells are then contacted with a peptide display library, and target peptides that specifically bind to the T cells are screened therefrom.

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.

The present application provides a pharmaceutical composition for preventing or treating cancer, including, as an active ingredient, a fusion protein dimer including an IL-2 protein or a variant thereof and a CD80 protein or a fragment thereof, and an immune checkpoint inhibitor. In one embodiment, the fusion protein including a CD80 fragment, an Fc domain of an immunoglobulin, and an IL-2 variant can activate immune cells such as natural killer cells, and control immune cell regulatory activity of regulatory T cells. Furthermore, the combined administration of the fusion protein and an immune checkpoint inhibitor such as Keytruda known as a PD-1 inhibitor can be effective in inhibiting cancer. Accordingly, the pharmaceutical composition provided by the present application including, as an active ingredient, a fusion protein dimer including an IL-2 protein or a variant thereof and a CD80 protein or a fragment thereof, and an immune checkpoint inhibitor can be effectively used for the treatment of cancer, and has a high degree of industrial applicability.

Provided is a method for screening polypeptides that specifically target T cells, comprising: providing T cells having a surface antigen marker selected from at least one of CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD16, CD25, CD26, CD27, CD28, CD30, CD38, CD39, CD40L, CD44, CD45, CD62L, CD69, CD73, CD80, CD83, CD86, CD95, CD103, CD119, CD126, CD150, CD152 (CTLA-4), CD153, CD154 (CD40L), CD161, CD183, CD223, CD254, CD275, CD45RA, CXCR3, CXCR5, FasL, IL18R1, CTLA-4, OX40, GITR, LAG3, ICOS, PD-1, leu-12, TCR, TLR1, TLR2, TLR3, TLR4, TLR6, NKG2D, CCR, CCR1, CCR2, CCR4, CCR6, and CCR7; and contacting the T cells with a polypeptide display library, and screening therefrom target polypeptides that specifically bind to the T cells.

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.

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 present disclosure provides pharmaceutical compositions comprising CD80 extracellular domain (ECD)-fragment crystallizable (Fc) fusion molecules. The present disclosure also provides methods for treating solid tumors by administering such pharmaceutical compositions.

The present invention relates to a composition comprising fusion molecules with the extracellular domain (ECD) of CD80 for use in the treatment of a PD-L1 negative tumor in a subject, wherein the CD80 ECF fusion molecules comprise a human CD80 ECD and a human IgG Fc domain.

The application provides an LNP-mRNA and connector macrophage for connecting T cells, macrophages and tumor cells and application thereof, and relates to the technical field of biotechnology.The mRNA of the chimeric antigen receptor of the application for targeting tumor cells, the mRNA of CD80 and the mRNA of the anti-CD3 single-chain antibody are wrapped by the lipid nanoparticles, three kinds of mRNA can be simultaneously delivered and are taken by macrophages and tumor cells, the engineered macrophages with the connector effect are formed, and then the macrophages, T cells and tumor cells are combined together and the T cells are activated.The macrophages and the activated T cells can synergistically play the tumor killing effect, meanwhile, the macrophages can also promote the formation of memory T cells, and realize long-term tumor monitoring and inhibition effect.Different from the existing connector, the existing connector is in the form of antibody, and the application is in vivo edited macrophages.

The present invention relates to the field of oncolytic viruses, and in particular to a recombinant rhabdovirus, such as a vesicular stomatitis virus encoding a CD80 ectodomain Fc fusion protein in its genome. The invention further relates to the use of the recombinant virus in the treatment of cancer, and also to methods for producing such viruses.

The present invention relates to a pharmaceutical formulation with enhanced stability of a fusion protein dimer comprising a modified IL-2 protein and a CD80 protein. The fusion protein dimer comprising an IL-2 protein and a CD80 protein can not only activate immune cells owing to IL-2, but also effectively regulate Treg cells owing to CD80. When the formulation according to the present invention is applied to a fusion protein dimer comprising an IL-2 protein and a CD80 protein, the stability of the fusion protein dimer is significantly increased, and it can be used as a liquid formulation. Accordingly, the commercial applicability of the fusion protein dimer can be increased.

The present invention provides a pharmaceutical composition for cancer treatment, comprising a fusion protein containing IL-2 protein and CD80 protein and an anticancer agent as active ingredients. One embodiment of the present invention, a fusion protein containing a CD80 fragment, immunoglobulin Fc, and an IL-2 variant, can activate immune cells such as natural killer cells and simultaneously suppress the immune cell-regulating activity of regulatory T cells. Furthermore, when administered in combination with an anticancer agent, the fusion protein can effectively suppress cancer. A pharmaceutical composition comprising a fusion protein containing IL-2 protein and CD80 protein and an anticancer agent as active ingredients increases immune activity in the body, making it effective for treating not only cancer but also infectious diseases, making it highly applicable industrially.

The invention discloses a cell model combination for detecting induced differentiation of macrophages by using secretory luciferase, and belongs to the technical field of cell models. The technical problem to be solved is that a method for noninvasively and specifically monitoring the polarization state of macrophages in real time on the cellular level is lacked. The key point of the technical scheme is that a cell model for detecting induced differentiation of macrophages is provided. Specifically, a CD80 promoter and a CD163 promoter are combined with secretory luciferase, the luciferase is expressed in THP-1 cells through a recombinant lentivirus transfection method to obtain a cell model, and the polarization state of macrophages can be detected by using the cell model.

The invention provides a monoclonal antibody targeting human HHLA2 and a multifunctional fusion antibody molecule derived from the monoclonal antibody, and relates to the field of biological medicine. The HHLA2 monoclonal antibody can be combined with an HHLA2 antigen with high specificity and effectively block an immunosuppression signal channel between the HHLA2 antigen and a receptor KIR3DL3, so that T cell function inhibition is relieved, and the tumor killing function of NK cells is promoted. Based on the antibody skeleton, a fusion antibody containing a plurality of immunomodulatory domains is constructed, and the domains include but are not limited to an anti-PD-L1 antibody or anti-PD-1 antibody or anti-CD3 antibody domain, a CD86 / CD80 variant polypeptide and an LAG3 variant polypeptide. The fusion antibody can cooperatively block a plurality of immune checkpoint pathways, activate a costimulatory signal, promote antigen presenting cell maturation, and enhance T cell activation and killing functions. The provided antibody molecule can be used for preparing immunotherapy drugs for various indications, is especially suitable for treating solid tumors or hematoma, and has remarkable application potential in the aspect of enhancing anti-tumor immune response.

The application relates to an application of artemisinin in tolerance DC cell culture, and provides a tolerance DC cell culture medium with artemisinin, which comprises a basic culture medium, cytokines and artemisinin, wherein the concentration of the artemisinin is 0.5-5 muM. The tolerance DC cell culture medium with artemisinin has reduced expression levels of co-stimulating molecules CD80, CD83, CD86 and HLA-DR, which indicates that the addition of artemisinin is beneficial to the tolerance DC cell culture.

Provided are a tolerogenic DC cells culture medium and the use thereof in tolerogenic DC cells culturing. The culture medium comprises: a basic culture medium, a cytokine, berberine, and autologous plasma, wherein the concentration of berberine is 0.25-5 μM, and the cytokine comprises 100-1000 U / mL GM-CSF, 10-50 ng / mL IL -4, and 100-1000 U / mL TGF-β. The expression levels of costimulatory molecules CD80, CD83, CD86 and HLA-DR of DC cells cultured by means of the culture medium are significantly reduced.