335 results about "CD28" 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.

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.

The present invention discloses a nano antibody against BCMA and its preparation method and application, and relates to the field of biomedical technology. The present invention uses CRISPR / Cas9 technology to knock out B2M and TRAC genes in T cells to prepare universal CAR-T cells; the nano antibody targeting BCMA and the natural ligand SIRPα extracellular N-terminal V region of CD47, the transmembrane region of CD28, the intracellular signal region of 4-1BB and the intracellular signal region of CD3ζ are connected in series to form a dual-targeted chimeric antigen receptor for the treatment of multiple myeloma, so as to solve the high recurrence problem faced by CAR-T cell therapy in the treatment of multiple myeloma. The universal CAR-T cells prepared by the present invention have strong killing activity against multiple myeloma cells, effectively improve the treatment effect, and provide a key material for the subsequent development of adoptive immunotherapy with high efficiency and lasting anti-tumor activity.

The invention belongs to the technical field of molecular biology, and particularly relates to an anti-CD28 nano antibody as well as a preparation method and application thereof. The preparation process of the anti-CD28 nano antibody provided by the invention comprises the following steps: constructing a CD28 antigen to immunize alpaca, performing phage library construction on the immunized alpaca PBMC, screening the phage library, and selecting a correct sequence to construct, express and purify; and finally obtaining the anti-CD28 nano antibody through cell function detection and screening. The nano antibody provided by the invention has specific recognition and binding capacity to CD28, and has the advantages of strong specificity, high sensitivity and the like; meanwhile, the development and production cost of the CD28 antibody is effectively reduced, and the antibody expression time is shortened.

The invention belongs to the technical field of molecular biology, and particularly relates to an anti-CD28 nano antibody as well as a preparation method and application thereof. The preparation process of the anti-CD28 nano antibody provided by the invention comprises the following steps: constructing a CD28 antigen to immunize alpaca, performing phage library construction on the immunized alpaca PBMC, screening the phage library, and selecting a correct sequence to construct, express and purify; and finally obtaining the anti-CD28 nano antibody through cell function detection and screening. The nano antibody provided by the invention has specific recognition and binding capacity to CD28, and has the advantages of strong specificity, high sensitivity and the like; meanwhile, the development and production cost of the CD28 antibody is effectively reduced, and the antibody expression time is shortened.

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 present invention provides an antibody composition for detecting multiple myeloma based on full-spectrum flow cytometry and its application, belonging to the technical field of multiple myeloma detection. The antibody composition includes CD3 antibody, CD20 antibody, HLA-DR antibody, CD8 antibody, CD11b antibody, CD10 antibody, CD71 antibody, CD28 antibody, CD14 antibody, CD13 antibody, Igκ antibody, CD15 antibody, Igλ antibody, CD117 antibody, CD56 antibody, CD45 antibody, CD19 antibody, CD34 antibody, CD138 antibody, CD4 antibody, CD38 antibody, CD22 antibody and CD27 antibody. The kit containing the antibody composition can be applied to a full-spectrum flow cytometer to accurately perform preliminary screening on patients with multiple myeloma.

The invention provides a culture method for inducing and amplifying central memory T cells with high expression of CD62L typing, which comprises the following steps: collecting peripheral blood mononuclear cells, adding the peripheral blood mononuclear cells into a culture medium containing stimulant CD3 / CD28 antibody coupling magnetic beads, amplifying for 7-12 days to obtain a cell population with TCM, and the culture medium further comprises IL-2, IL-7, IL-15 and syringaresinol. The method can effectively improve the TCM cell content and purity of the high-expression CD62L marker, and can be effectively used for treating tumors, infection or other immune related diseases.

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 the technical field of tumor immunotherapy, in particular to a dual-targeting chimeric antigen receptor, a recombinant expression vector, an anti-tumor natural killer cell and application, and provides a PD1-DAP10-41BB-P2A-NKG2D-Ig4-CD28-41BB-CD3 zeta fusion receptor.The dual-targeting chimeric antigen receptor can target PD-L1 on the surface of a tumor cell, can also recognize NKG2DLs and can be used for preparing anti-tumor natural killer cells. The broad spectrum of the NK cells is greatly improved, and meanwhile, the immune escape of tumor cells is also reduced.

The invention provides an anti-CD28 humanized single-domain antibody and a preparation method of the anti-CD28 humanized single-domain antibody. Specifically, the invention discloses a plurality of single-domain antibodies targeting CD28, humanized antibodies thereof, derived proteins, gene sequences for encoding the single-domain antibodies and the humanized antibodies, and expression vectors and expression systems for producing the single-domain antibodies and the humanized antibodies. The single-domain antibody provided by the invention is a CD28 non-agonistic antibody, can block the binding of CD28 and CD80, and can specifically bind to CD28 of human and monkeys. The single-domain antibody provided by the invention has high safety, and provides a research and development basis for development of antibody coupling drugs and multispecific antibody drugs. A bispecific antibody composed of the CD28 single-domain antibody and the targeting tumor antigen antibody can significantly enhance the activity of the CD3 bispecific antibody. The activity of a multi-specific antibody composed of the CD28 single-domain antibody, the targeting tumor antigen antibody and the CD3 antibody is significantly superior to that of the CD3 bispecific antibody.

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 invention relates to an induction medium and an expansion medium for inducing and amplifying TIL cells from tumor tissues, and a method for inducing and / or amplifying TIL cells. The induction medium comprises one or two selected from IL-7 and IL-15, IL-2, TNF-α, CD3 antibody and CD28 antibody. The expansion medium comprises one or two selected from IL-7 and IL-15, IL-2, TNF-α, CD3 antibody, CD28 antibody and CD137 antibody.

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.

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.

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 present disclosure provides methods for treating, reducing the severity, 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 prostate- specific membrane antigen (PSMA) and CD28 as monotherapy or in combination with an anti-PDl antibody.

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 present invention relates to antibody arms that bind to human CD28 agonists. The present invention relates to bispecific antibodies that bind to human carcino-embryonic antigen (CEA) and human CD28 using the agonist anti-CD28 arm described herein. The present invention relates to bispecific antibodies that bind to human mesothelin (MSLN) and human CD28 with the anti-CD28 arm using the agonist described herein.

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.