226 results about "CD28" patented technology

Disclosed are lipid nanoparticle (LNP) delivery systems that specifically target T cells. The LNP delivery system comprises antibodies conjugated to the surface of the LNP, e.g., via maleimide chemistry, that target at least two T cell surface proteins, e.g., CD3 and CD28. The LNP delivery system can have a single population of LNP conjugated to either a bispecific antiCD3 / antiCD28 antibody, or two monospecific antiCD3 and antiCD28 antibodies, or two populations of LNP wherein each population comprises a monospecific antibody. The payload of the LNP delivery system can be, e.g., mRNA encoding chimeric antigen receptors (CAR), a linear DNA fragment or a plasmid encoding chimeric antigen receptors (CAR) or therapeutic proteins such as antibodies, components of a gene editing systems (e.g., CRISPR-Cas), small molecules, antibody-drug conjugates (ADC), and any combination thereof, either encapsulated in the LNP or attached to its surface (e.g., conjugated). Also provided are lipids, pharmaceutical compositions, kits, and methods of treatment.

Disclosed herein are isolated polypeptide and polypeptide complex compositions that comprise a first antigen recognizing molecule that binds to CD28 and a second antigen recognizing molecule that binds to prostate-specific membrane antigen (PSMA).

The invention relates to the technical field of biology, in particular to a tri-specific antibody based on structure optimization protein activity and application of the antibody. Specifically, the invention relates to a trispecific antibody specifically combined with Her2, CD3 and CD28, and the Her2 / CD3 / CD28 trispecific antibody comprises a Fab part of a monoclonal antibody specifically combined with CD3, an antibody fragment specifically combined with Her2 and an antibody fragment specifically recognized with CD28. The invention also relates to an application of the antibody in preparing a medicine for treating cancers, and the antibody plays an important role in treating human tumors.

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.

Provided herein are trispecific and / or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more target proteins, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation, and wherein and a second pair of polypeptides possess a single variable domain forming a single antigen binding site. In some embodiments, the binding proteins comprise a binding site that binds a CD28 polypeptide, a binding site that binds a CD3 polypeptide, and a binding site that binds a third polypeptide, such as a tumor target protein. In some embodiments, the binding proteins comprise four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins. The disclosure also relates to methods for making trispecific and / or trivalent binding proteins and uses of such binding proteins.

The present disclosure relates to anti-CD28 antibodies that bind to human CD28 and antigen-binding fragments thereof, compositions comprising same, and uses thereof in delaying and / or preventing tumor growth.

To provide trispecific and / or trivalent binding proteins.SOLUTION: Disclosed herein is a trispecific and / or trivalent binding protein comprising four polypeptide chains that form three antigen binding sites that specifically bind to one or more target proteins, where a first pair of the polypeptides that form the binding protein possesses double binding domains having crossover tropism, and a second pair of the polypeptides has a single variable domain that forms a single antigen binding site. In some embodiments, the binding protein comprises a binding site that binds to CD28 polypeptide, a binding site that binds to CD3 polypeptide, and a binding site that binds to a third polypeptide that binds to, for example, a tumor targeting protein.SELECTED DRAWING: Figure 1A

Disclosed are lipid nanoparticle (LNP) delivery systems that specifically target T cells. The LNP delivery system comprises antibodies conjugated to the surface of the LNP, e.g., via maleimide chemistry, that target at least two T cell surface proteins, e.g., CD3 and CD28. The LNP delivery system can have a single population of LNP conjugated to either a bispecific antiCD3 / antiCD28 antibody, or two monospecific antiCD3 and antiCD28 antibodies, or two populations of LNP wherein each population comprises a monospecific antibody. The payload of the LNP delivery system can be, e.g., mRNA encoding chimeric antigen receptors (CAR), a linear DNA fragment or a plasmid encoding chimeric antigen receptors (CAR) or therapeutic proteins such as antibodies, components of a gene editing systems (e.g., CRISPR-Cas), small molecules, antibody-drug conjugates (ADC), and any combination thereof, either encapsulated in the LNP or attached to its surface (e.g., conjugated). Also provided are lipids, pharmaceutical compositions, kits, and methods of treatment.

Provided herein are trispecific and / or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more target proteins, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation, and wherein and a second pair of polypeptides possess a single variable domain forming a single antigen binding site. In some embodiments, the binding proteins comprise a binding site that binds a CD28 polypeptide, a binding site that binds a CD3 polypeptide, and a binding site that binds a third polypeptide, such as a tumor target protein. In some embodiments, the binding proteins comprise four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins. The disclosure also relates to methods for making trispecific and / or trivalent binding proteins and uses of such binding proteins.

A chimeric antigen receptor is disclosed that includes: (a) an extracellular high affinity streptavidin; (b) a hinge domain from CD8; (c) a CD28 transmembrane domain; (d) an intracellular 4-1BB and / or CD28 signaling domain; and (e) an intracellular CD3 zeta signaling domain, wherein (a)-(e) are in N-terminal to C-terminal order. Nucleic acids encoding this chimeric antigen receptor, and T and natural killer (NK) cells transformed with this chimeric antigen receptor are also disclosed. The use of this chimeric antigen receptor for the treatment of tumors is also disclosed.

The application provides guidance and navigation control (GNC) proteins. In one embodiment, the GNC protein Comprises a T-cell binding moiety and a cancer-targeting moiety, wherein the T-cell binding moiety has a binding specificity to a T-cell receptor comprising CD3, CD28, PDL1, PD1, OX40, 4-1BB, GITR, TIGIT, TIM-3, LAG-3, CTLA4, CD40, VISTA, ICOS, BTLA, Light, NKp30, CD28H, CD27, CD226, CD96, CD112R, A2AR, CD160, CD244, CECAM1, CD200R, TNFRSF25 (DR3), or a combination thereof, and wherein the cancer targeting moiety has a binding specificity to a cancer cell receptor.

Disclosed herein are multi-valent, multi-specific, single-chain antibodies with specificities for four antigens selected from EGFR, PD-L1, HSA, CD28, CD3E, OX-40, CD40, 4-1BB, LAG3, and CD16A.

The invention discloses a progressive multiple sclerosis differential diagnosis marker based on immunophenomics and application of the progressive multiple sclerosis differential diagnosis marker. The invention specifically provides an immune biomarker set for identifying progressive or recurrent remission type multiple sclerosis and a corresponding reagent and kit thereof. The immune biological marker provided by the invention comprises one or more of the following groups: a) activating a T cell subset; b) a CD28 < + > and CD28-T cell subset; c) forming a subgroup by the CD8 + T cells; and d) a MAIT cell subset category. The immune biomarker disclosed by the invention can also be applied in a multi-index combination manner, and can be applied to a) multiple sclerosis patients which are not subjected to disease modification treatment; b) a patient with multiple sclerosis treated by disease modification; and c) a very good effect of distinguishing clinical subtypes of the multiple sclerosis can be achieved in the three types of people of the multiple sclerosis patients who do not distinguish whether the multiple sclerosis patients are subjected to the disease modification treatment or not.

The application relates to a hybridoma cell strain 1B6A2 secreting an anti-fish T lymphocyte surface membrane protein CD28 monoclonal antibody, the hybridoma cell strain 1B6A2 is preserved in the China Center for Type Culture Collection (CCTCC), and the preservation number is CCTCC NO: C202291, and the preservation date is May 5, 2022. The application provides a powerful tool for simulating a second signal in vitro and exploring a CD28-mediated T cell adaptive immune response mechanism.

The invention relates to the field of biological medicine, and discloses an anti-tumor combined drug, the anti-tumor combined drug comprises a two-factor oncolytic virus and an HER2 CAR-T cell, the two-factor oncolytic virus is an OV-OX40L / IL12 oncolytic virus capable of simultaneously expressing OV-OX40L and IL12, the HER2 CAR-T cell is a cell specially targeting an HER2 antigen, and the CAR structure contained in the HER2 CAR-T cell comprises Anti-HER2 scfv, CD8hinge, CD8TM, CD28-4-1BB, CD3zeta, IRES and EGFP. The CAR-T therapy and the oncolytic virus therapy are combined, the advantages of the CAR-T therapy and the oncolytic virus therapy are mutually promoted, the infiltration and the activity of the CAR-T cells in solid tumors are enhanced by the two-factor oncolytic viruses, and meanwhile, the oncolytic virus-mediated oncolytic property can be improved by the CAR-T cells.

The invention belongs to the field of biological medicine, and relates to a method for preparing iTNK cells, prepared iTNK, a pharmaceutical composition of the iTNK and application of the iTNK. Specifically, the invention relates to a method for preparing iTNK cells, which comprises the following steps: (1) adding a proper amount of anti-CD3 / CD28 / CD2T cell Activator into a culture medium for culturing T cells; culturing for 1-4 days; preferably culturing for 2 days; (2) replacing the culture medium with a culture medium which does not contain anti-CD3 / CD28 / CD2T cell Activator, and continuously culturing for 20 to 30 days; preferably, the culture lasts for 26 days. The iTNK cell prepared by the method disclosed by the invention has dual attributes of cytotoxic T cells and NK cells and a tumor killing function, and has a good anti-tumor application prospect.

Provided are trispecific T Cell Engagers or TSMAb's, antibodies that can simultaneously engage three different types of epitopes on the same target or on different targets. More specifically, the invention is directed to trispecific molecules that bind to DLL3, MUC17 or CLDN18.2 and activate CD (cluster of differentiation) molecules (e.g. CD3, CD28 and CD137). Also provided are methods of treating an ailment such as cancer using an antibody (or fragment) against DLL3, MUC17 or CLD18 paired with an antibody (or fragment) of an agonist antibody that activates CD3, CD28 and / or CD137.

The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that binds specifically to human CD28, and a second antigen-binding domain that binds specifically to human MUC16. In certain embodiments, the bispecific antigen-binding molecules of the present invention can inhibit the growth of tumors expressing MUC16, such as ovarian tumors. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is convenient and / or therapeutically beneficial.

The present invention discloses a monoclonal antibody against CD28 and cells, belonging to the field of biotechnology. The present invention provides the amino acid sequences of the CDR regions of the monoclonal antibody against CD28, namely the CDR regions of the heavy chain variable region and the light chain variable region, specifically the amino acid sequences of heavy chain variable region CDR1, 2, 3 shown in SEQ ID NO:1, 2, 3, and the amino acid sequences of light chain variable region CDR1, 2, 3 shown in SEQ ID NO:9, STS, SEQ ID NO:10.

Provided is a method of treating cancer in an individual by administering to the individual modified cells that express a chimeric antigen receptor (CAR) that contain a TIGIT extracellular domain that can bind to poliovirus receptor (PVR), a CD28 segment, and a CD3ζ segment. The modified cells may co-express and secrete a Bi-specific T cell engager (BiTE). The BiTE includes a segment that can specifically bind to human Folate Receptor alpha (FRα) and a segment that that can specifically bind to a human CD3□ segment. Modified cells that express the CAR, and may also express and secrete the BiTE, and polynucleotides encoding the CAR and the BiTE, are also provided.

Provided are bispecific T Cell Engagers. More specifically, the invention is directed to bispecific molecules that bind to DLL3, MUC17 or CLD18 and activate CD (cluster of differentiation) molecules (e.g. CD3, CD28 and CD137). Also provided are methods of treating an ailment such as cancer using an antibody (or fragment) against DLL3, MUC17 or CLD18 paired with an antibody (or fragment) of an agonist antibody that activates CD3, CD28 and / or CD137.

The present disclosure provides methods for treating prostate cancer or metastatic castration-resistant prostate cancer, reducing the severity of prostate cancer or metastatic castration-resistant prostate cancer, or inhibiting the growth of prostate cancer or metastatic castration-resistant prostate cancer. The methods of the present disclosure comprise administering to a subject in need thereof a therapeutically effective amount of a bispecific antibody, or antigen-binding fragment thereof, that specifically binds to prostate specific membrane antigen (PSMA) and CD28, as a monotherapy or in combination with an anti-PD1 antibody.

The present application relates to a kind of based on logic gate double-target point chimeric antigen receptor modified TIL cell, lentivirus expression vector and application, belong to tumor immunotherapy and gene editing technical field.The TIL cell based on logic gate double-target point chimeric antigen receptor modified in the application, double-target point chimeric antigen receptor includes chimeric antigen receptor EGFR and chimeric antigen receptor GD2;Chimeric antigen receptor EGFR is composed of CD8 alpha signal peptide, anti-EGFR single-chain antibody, CD8 alpha transmembrane region, 4-1BB costimulatory domain and CD3 zeta intracellular signal domain in series;Chimeric antigen receptor GD2 is composed of CD8 alpha signal peptide, anti-GD2 single-chain antibody, CD28 transmembrane region, CD27 costimulatory domain and CD3 zeta intracellular signal domain in series.The present application solves the defects that lentivirus transduction targeting is poor in prior art, CAR signal activation specificity is insufficient, TIL cell is easily exhausted, has the advantages that gene integration is accurate, signal transduction is controllable, in-vivo survival time is long, can be efficiently used for the immunotherapy of double-antigen co-expression solid tumor.

The present disclosure relates to methods of treating or inhibiting the growth of a tumor, wherein the methods include selecting a subject with cancer and administering to the subject in need thereof a therapeutically effective amount of a cancer vaccine (e.g., mRNA vaccine against a tumor) in combination with a bispecific antigen-binding molecule comprising a first antigen-binding domain that binds specifically CD28 and a second antigen-binding domain that binds specifically to a tumor-associated antigen (TAA). The combination therapy demonstrates increased anti-tumor efficacy, increased duration of tumor control and / or increased overall survival, as compared to a subject administered the cancer vaccine as monotherapy.

To provide a method for enriching immune-effector cells suitable for use in a CART cell therapy.SOLUTION: The method comprises: (a) obtaining immune effector cell populations from a cancer patient in need of a CART cell therapy; (b) selecting an immune effector cell population comprising a plurality of markers selected from the group consisting of CCR7, CD62L, CD45RO and CD95; (c) generating a regulatory T cell-depleted immune effector cell population; (d) removing immune effector cells expressing a tumor antigen expressed in the cancer patient to form regulatory T cell-depleted and tumor antigen-depleted immune effector cell population; and (e) selecting a regulatory T cell-depleted and tumor antigen-depleted immune effector cell population expressing a plurality of markers selected from the group consisting of CD3, CD28, CD4, CD8, CD45RA and CD45RO thereby forming an enriched immune effector cell population suitable for a CART cell therapy.SELECTED DRAWING: None

Provided herein are multispecific binding proteins comprising (a) a first antigen binding domain (ABD) comprising an immunoglobulin single variable domain (ISVD) (e.g., VHH) having binding specificity for CD28; and (b) a second ABD comprising an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL) having a binding specificity for OX40. Methods of treating autoimmune diseases with the multispecific binding proteins are also provided.

The present invention relates to PD-L1xCD28 bispecific antibodies that act as immune checkpoint inhibitors by binding and blocking PD-L1 (thus preventing it from binding to PD-1 expressed on T cells) and can further deliver a co-stimulatory signal to T cells by aggregating and competitively binding to CD28.

Multispecific antibodies that bind to an effector associated antigen (EAA), such as CD28, and a disease associated antigen (DAA), such as Nectin-4, are provided, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and their use to treat disorders, such as cancer, where modulation of effector cell activity against target cells can be used as a treatment modality.

The application relates to the diagnosis and treatment of diseases, including cancer, chronic infectious diseases, autoimmune diseases, inflammatory disorders, as well as the prevention of transplant rejection. The invention provides, and involves the use of, antibody molecules that bind CD28 in a non super-agonistic manner and which also bind to CTLA-4. The antibody molecules may form part of a bispecific molecule which binds e.g. a tumor associated antigen or a further T cell antigen, such as CD3.

The invention discloses application of a peripheral T lymphocyte index in preparation of a coronary heart disease risk assessment kit, the kit and a method. Prediction indexes of the kit comprise four T lymphocyte subgroups: CD3 + CD8 + CD28-, CD3 + CD8 + HLADR +, Tc1, CD3 + gamma delta + V delta 2 + NKG2D +. The invention finds that the four novel lymphocytes in the peripheral blood are risk factors of the coronary heart disease for the first time, and the four risk factors are combined as a combined prediction index. The kit has an optimal effect on evaluating the risk of the coronary heart disease, and has a wide application prospect in the aspect of predicting the risk of the coronary heart disease.