114 results about "CD28" patented technology

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.

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.

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.

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 present disclosure relates to methods of culturing immune cells, e.g., T cells, NK cells, and / or TILs, for an immune cell therapy, wherein the immune cells are contacted with a CD28 agonist, and wherein the immune cells are not contacted with a CD3 agonist. In some aspects, the methods disclosed herein promote the enrichment of immune cells having a less-differentiated phenotype, i.e., expressing markers characteristic of stem cell-like memory T (Tscm) cells. Cells cultured using the methods disclosed herein can be used for various cell therapies, including but not limited to chimeric antigen receptor (CAR) T cell therapy and TCR T cell therapy, including neoantigen directed-T cell therapies.

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.

Disclosed herein are monospecific and multispecific antibodies specific for CD28 and CD3E, and one or more of OX-40, CD40, 4-1BB, HSA, IL-22, PD-L1, CD16, CD47, CD33, LAG3, and EGFR.

The invention discloses a CD8 + T cell culture solution and application thereof. The cell culture solution comprises an induction culture solution and an amplification culture solution, wherein the amplification culture solution comprises a basic culture medium, and the basic culture medium contains ginsenoside with the final concentration of 20-100 [mu] g / mL, concanavalin A with the final concentration of 20-100 [mu] g / mL and IL-2 with the final concentration of 100-1000 U / mL; the induction culture solution is based on an amplification culture medium, and a CD3 antibody with the final concentration of 50-100 ng / mL and a CD28 antibody with the final concentration of 50-100 ng / mL are added. The ginsenoside component in the CD8 + T cell culture fluid can induce and stimulate PBMC to be differentiated into CD8 + T cells, and concanavalin A cooperates with ginsenoside to promote rapid amplification and growth of the CD8 + T cells; meanwhile, the cell culture method is simple to operate and low in cost, and has certain universality.

The anti-CD40L / anti-CD28 bispecific antibody according to the present application comprises anti-CD40L scFv and anti-CD28 scFv, and thus does not exhibit a thromboembolic side effect, can exhibit an excellent effect of treating autoimmune diseases and / or graft versus host diseases while preventing a T cell activation effect caused by CD28 dimer formation, and can be used as a novel anti-CD40L / anti-CD28 bispecific antibody. In addition, excellent bispecific antibody physical characteristics can be shown.

The invention relates to the technical field of biological medicine, and particularly discloses a chimeric antigen receptor of a targeted NKG2D ligand, a nucleic acid molecule, an expression vector, a macrophage and a preparation method and application of the chimeric antigen receptor, the nucleic acid molecule, the expression vector and the macrophage, and an extracellular antigen binding domain is an NKG2D extracellular structural domain; the hinge region is a CD28 hinge region or a CD8a hinge region; the transmembrane / intracellular signal transduction structural domain is an FCGR1 transmembrane / intracellular signal transduction structural domain or a CD3z transmembrane / intracellular signal transduction structural domain. The chimeric antigen receptor provided by the invention specifically recognizes and is combined with NKG2DLs highly expressed in NKG2DL positive malignant tumors, and macrophages expressing the chimeric antigen receptor can directly swallow tumor cells, promote M1 type polarization, reprogram tumor microenvironment and induce recruitment and activation of T cells, so that effective treatment of the malignant tumors is realized.

The application discloses a kind of FAP targeted chimeric antigen receptor regulatory T cells, its preparation method and application, belong to biomedical technology field.The FAP targeted chimeric antigen receptor regulatory T cell contains chimeric antigen receptor, the chimeric antigen receptor includes single-chain antibody targeted to FAP, CD8 alpha hinge region, CD8 transmembrane region, CD28 signal region and CD3 zeta signal region, its nucleotide sequence is as shown in SEQ ID NO.1.The FAP targeted chimeric antigen receptor regulatory T cell can effectively accumulate in damaged heart, and control the excessive fibrosis and inflammatory response in MI, which not only highlights the therapeutic potential of CAR Tregs against FAP in promoting heart healing, but also lays the foundation for CAR Treg treatment in clinical environment of severe MI.

The application provides anti-CD28 nanobodies and uses thereof, and belongs to the technical field of biotechnology. Specifically disclosed are several CD28-targeted nanobodies, coding sequences and expression vectors for producing the nanobodies, and application of the nanobodies in preparation of tumor treatment drugs. The nanobodies can not only specifically recognize and bind to CD28, laying a foundation for subsequent development of antibody conjugated drugs and multi-specific antibodies, but also can be combined with tumor antigen-targeted antibodies to form multi-specific antibodies, and the formed multi-specific antibodies significantly enhance the ability of activated T cells and the activity of killing tumor cells.

Provided is a fusion polypeptide. The polypeptide contains a first domain, a second domain and a third domain, wherein the first domain is capable of binding to CD3, the second domain is capable of binding to a tumor-associated antigen (TAA), and the third domain is capable of binding to CD28 and / or CTLA4.

The present invention relates to PD-1-CD28 fusion proteins, nucleic acid molecules, vectors, transduced cells carrying nucleic acid molecules or vectors of the present invention or expressing the fusion proteins of the present invention, methods and kits comprising the nucleic acid molecules, vectors and / or the fusion proteins of the present invention. The invention also provides the use of said transduced cells in a method for the treatment of particular diseases as well as a pharmaceutical composition / medicament comprising said transduced cells expressing the fusion proteins of the present invention for use in a method of treating of diseases, in particular in the medical intervention of diseases characterized by PD-L1 and / or PD-L2 expression.

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).

The application belongs to the technical field of molecular biology, and particularly relates to an anti-CD28 nanobody and a preparation method and application thereof. The anti-CD28 nanobody provided by the application is prepared in the following manner: constructing a CD28 antigen to immunize a llama, constructing a phage library to the PBMC of the immunized llama, screening the phage library, selecting correct sequences to construct and express and purify, and finally obtaining the anti-CD28 nanobody through cell function detection screening. The nanobody provided by the application has specific recognition and binding capacity for CD28, has the advantages of high specificity, high sensitivity and the like, effectively reduces the development and production cost of the CD28 antibody, and shortens the expression time of the antibody.

The present invention provides a multifunctional molecule comprising an agonistic anti-CD28 binding domain covalently linked to another binding moiety that binds to a target specifically expressed on T cells surface, and uses thereof.

Methods of decreasing shedding of CD28, decreasing soluble CD28 levels, treating cancer and improving immunotherapies comprising inhibiting matrix metalloproteases are provided. Methods of producing agents for performance of the methods of the invention are also provided.

The present invention relates to the use of a trispecific antibody that specifically binds to CD19, CD3 and CD28 in the preparation of a drug for treating an autoimmune disease, wherein the autoimmune disease is an autoimmune disease based on a B cell, in particular an autoimmune disease based on an autoreactive B cell.

The invention relates to the technical field of prevention and treatment of complications after organ transplantation, and discloses a preparation for preventing and treating diabetes mellitus after organ transplantation based on a Treg cell metabolic regulation function and application, the preparation takes repair or enhancement of the Treg cell metabolic regulation function as a core action mechanism, and comprises at least one active component, according to the PTDM prevention and treatment preparation based on the Treg cell metabolic regulation function and the application, the preparation contains IL-2 / anti-CD3 / CD28 beads, FKBP12siRNA, a PPAR-gamma agonist, SOCS-3siRNA and other active ingredients, and the active ingredients are matched with pharmaceutical auxiliary materials to be prepared into an injection or a freeze-dried powder injection; the preparation is suitable for PTDM high-risk recipients using CNI after kidney / heart transplantation, has a single drug and combination scheme, can also amplify Treg cells in vitro for transfusion to assist intervention, can realize'immune tolerance-metabolic regulation 'double-effect synergy, accurately target PTDM key pathways, adapt to multiple transplantation types, and can be combined with CPB for blood perfusion to synergistically reduce PTDM and AKI risks, reduce non-target injury and improve the curative effect of the PTDM. The life quality of a recipient is improved, the medical burden is reduced, and the blank of PTDM immunotherapy is filled.

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.

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 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 present invention relates to bispecific agonist CD28 antigen-binding molecules characterized by monovalent binding to CD28, including a novel humanized EpCAM antibody, methods for their production, pharmaceutical compositions containing these antibodies, and methods of using them.

The invention belongs to the technical field of cell biology, and particularly relates to a culture medium for amplifying Treg cells, a culture method and application. The culture medium comprises an activation culture medium and an amplification culture medium, wherein the activated culture medium is prepared from a serum-free culture medium, IL-2 (Interleukin-2), TGF (Transforming Growth Factor)-beta (beta), rapamycin, IL-27 (Interleukin-27), retinoic acid and Anti-Human CD3 / CD28 beads; the amplification culture medium comprises a serum-free culture medium, IL-2, rapamycin and IL-27. According to the invention, the culture medium combination with a specific formula and proportion is adopted, and the synergistic effect of the IL-2, the TGF-beta, the rapamycin, the IL-27, the retinoic acid and the Anti-Human CD3 / CD28 beads is utilized, so that the amplification multiple and the immunosuppression capability of the Treg cells are remarkably improved. The invention provides a more efficient and safer technical scheme for clinical application of Treg cell therapy.

The invention relates to a PD1-CD28 chimeric signal conversion receptor and application of the PD1-CD28 chimeric signal conversion receptor in immune cell therapy, and particularly discloses a fusion protein containing a PD-L1 binding region derived from PD1 and a hinge region, a transmembrane region and an intracellular region derived from CD28, homodimers formed by the fusion protein, nucleic acid encoding the fusion protein and a carrier containing the nucleic acid. Also disclosed are immune cells, vector systems, compositions and kits that co-express the fusion proteins and chimeric antigen receptors (CARs), as well as methods of using the immune cells and vector systems to treat diseases in a subject.