220 results about "CD40" patented technology

Provided herein are methods of inserting a nucleic acid encoding a polypeptide of interest into a target genomic locus in a cell or a population of cells in a subject, methods of expressing a polypeptide of interest from a target genomic locus in a cell or a population of cells in a subject, methods of treating an enzyme deficiency in a subject in need thereof, and methods of preventing or reducing the onset of a sign or symptom of an enzyme deficiency in a subject in need thereof. The methods use CD40 inhibitors (e.g., CD40 antigen-binding molecules) to mitigate immune response and facilitate redosing of nucleic acid constructs encoding a polypeptide of interest and nuclease agents targeting a target genomic locus to achieve, for example, a step-wise increase in expression of a polypeptide of interest in a subject following insertion of the nucleic acid construct without overshooting.

Disclosed herein are monospecific and multi-specific antibodies with specificities for one or more of OX40, CD40, 4-1BB, HSA, IL-22, or EGFR. Specifically, the disclosure provides variable heavy (VHH) domains of the antibodies with specificities for one or more of OX40, CD40, 4-1BB, HSA, IL-22, or EGFR, and associated sequences. Further discloses are methods of using the monospecific or multi-specific antibodies for treating ah autoimmune disease.

The present invention provides CD40 agonist antibodies having significantly higher CD40 activating activity in the presence of simultaneous tumor associated antigen (TAA) binding than in the absence of such simultaneous binding. Such TAA-dependent CD40 agonism results in a significant increase in therapeutic index, reducing or completely eliminating adverse events that are typically associated with CD40 activation, such as cytokine release syndrome or hepatotoxicity. Also provided are bispecific and multispecific antibodies and polypeptides such as 5T4 / CD40, such as chimeric antigen receptors, which are optionally incorporated into the antibodies with anti-TAA units. Methods of using these antibodies or polypeptides to treat and diagnose diseases, such as cancer, are also provided.

The present invention inter alia relates to a T-cell expressing a chimeric CD 95 receptor comprising a polypeptide, wherein said polypeptide comprises at least one CD 95-derived polypeptide region having at least 60% sequence identity with a polypeptide domain, a polypeptide region or a polypeptide motif of a human CD 95 wildtype receptor, wherein said human CD 95 polypeptide region comprises a CD 95 extracellular ligand binding domain; further wherein said polypeptide comprises at least one non-CD 95-derived co- stimulatory cytoplasmic polypeptide domain, region or motif of a tumor necrosis factor receptor superfamily protein comprising CD40, CD40L, CD27, HVEM, GITR, CD30, OX40, and / or LTBR, an immunoglobulin superfamily (IgSF) protein, a Toll-like-receptor, and / or an IL6-receptor family protein; wherein the T-cell further expresses an engineered T-cell receptor. The present invention also relates to a vector comprising nucleic acids encoding for the CD 95 receptor and the engineered T-cell receptor, as well as to a kit for preparing the T-cells of the present invention, and a pharmaceutical composition comprising the T-cells. The invention also relates to a method for preparing a T-cell for immunotherapy, and to a method for treating a patient having a disease comprising administering the pharmaceutical composition.

The invention provides a culture medium and a culture method for culturing human primary B lymphoma cells. The culture medium for culturing the human primary B lymphoma cells, disclosed by the invention, is prepared from an anti-immune globulin M antibody, a recombinant human CD40 ligand, CpG oligodeoxynucleotide 2006, superoxide dismutase, interleukin-2, interleukin-21 and interleukin-4. By using the culture medium and the culture method disclosed by the invention, effective and rapid amplification of the B lymphoma cells can be realized, the B lymphoma cells obtained by amplification maintain pathological characteristics of patients, the culture success rate and the amplification rate of the B lymphoma cells are improved, and a research basis can be provided for personalized treatment of the patients. The invention also provides B lymphoma cells obtained by in-vitro culture of the culture medium, and a method and application of the B lymphoma cells in curative effect evaluation and screening of drugs.

The present invention discloses an enhanced tumor vaccine adjuvant, and specifically relates to the field of vaccine adjuvants, the adjuvant comprising granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-2 (IL-2), interleukin-9 (IL-9), gamma interferon (IFN-γ) and at least one additional immunomodulatory factor, wherein the immunomodulatory factor is selected from tumor-specific antigen WT1, CD40 ligand (CD40L), Toll-like receptor agonist or a combination thereof. The tumor vaccine adjuvant of the present invention can enhance the body's immune response to the tumor vaccine and improve the prevention and treatment effect of the tumor vaccine on tumors.

The invention provides an anti-CD40 monoclonal antibody and application of the anti-CD40 monoclonal antibody. The anti-CD40 monoclonal antibody comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) as shown in SEQ ID NOs: 1-3, and three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) as shown in SEQ ID NO: 4, YAS and SEQ ID NO: 5. The antibody has binding activity with in-vitro CD40 and CD40 on the cell surface, and can be competitively bound with CD40L to block binding of the antibody and CD40L so as to inhibit CD40 / CD40L signal transduction and inhibit B cell proliferation and activation, so that immune overexpression and rejection can be inhibited. Therefore, when the antibody is applied to preparation of drugs for treating immune diseases, the antibody has the advantages of high targeting specificity, high affinity, few side effects and the like, and has a great application prospect.

Provided herein are methods and compositions for treating kidney-related diseases disorders, and complications, such as Berger's disease and for preventing transplant rejections. For example, the present disclosure describes methods of improving transplanted kidney function in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that specifically binds CD40 ligand.

The present invention relates to the technical field of molecular biology, and in particular, to an anti-CD40 nanobody, and a preparation method therefor and use thereof. The anti-CD40 nanobody provided by the present invention has three unique complementarity determining regions, namely CDR1, CDR2, and CDR3. The present invention further provides a sequence encoding the nanobody or its VHH chain, a corresponding expression vector, and a host cell capable of expressing the nanobody. The present invention includes immunizing an alpaca by constructing a CD40 antigen to obtain a PBMC of the alpaca and constructing a vector; screening an anti-CD40 antibody through phage display; and finally obtaining a highly sensitive and specifically binding antibody through functional assays and sequencing result analysis. The nanobody provided by the present invention can specifically recognize and bind to CD40.

The invention relates to the field of cell engineering, in particular to application of CD40 in promoting cell production and / or exosome release. According to the invention, after a lentiviral vector overexpressing the CD40 gene is constructed, the lentiviral vector transfects tumor cells, and finally the tumor cell strain stably expressing CD40 is obtained. Through extraction and detection, the cell strain obviously improves the yield of the exosome in unit cell and unit culture medium volume, and the yield of the exosome is obviously improved.

Provided are CD40-targetting antibodies and uses thereof. Provided are novel antigen-binding proteins that specifically bind CD40and antigen-binding fragments thereof. Provided are also fusion proteins comprising a first domain that activates an antigen-presenting cell (APC) (e.g., a dendritic cell) and a second domain that activates an immune effector cell (e.g., a T cell), wherein the first domain comprises antigen-binding proteins that specifically bind CD40 or antigen-binding fragments thereof disclosed herein.

The present invention inter alia relates to a chimeric transmembrane receptor comprising a polypeptide, wherein the polypeptide comprises at least one T cell immunoreceptor with Ig and ITIM domains (TIGIT) polypeptide region comprising a TIGIT extracellular ligand binding domain; further wherein the polypeptide comprises at least one non-TIGIT polypeptide region, wherein the at least one non-TIGIT polypeptide region comprises a transmembrane polypeptide region of CD2, CD40, HVEM, or CD30, and wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2, CD40, HVEM, or CD30, or wherein the transmembrane domain is from TIGIT and further wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2 or CD28. The invention also relates to corresponding nucleic acids, vectors and T-cells comprising or expressing the chimeric receptors, to a pharmaceutical composition comprising the T-cells, and to methods for preparing a T-cell for immunotherapy and for treating a disease, respectively, wherein the chimeric transmembrane receptor is used.

The present disclosure relates to multispecific proteins comprising designed ankyrin repeat domains with binding specificity for different targets, such as, e.g. CD40 and FAP. In addition, the present disclosure relates to nucleic acids encoding such multispecific proteins, pharmaceutical compositions comprising such multispecific proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods for treating or diagnosing diseases, such as cancer, in a mammal, including a human.

The present invention relates to a novel anti-CD40 antibody and use thereof and, more specifically, to a novel anti-CD40 antibody and use thereof, wherein the antibody comprises a complementarity determining region of a specific sequence and exhibits an excellent antagonistic effect by blocking CD40-CD40L signaling. The novel anti-CD40 antibody of the present invention exhibits an excellent antagonistic effect by blocking CD40-CD40L signaling, and thus can be widely used as a preparation for preventing or treating various diseases, such as autoimmune diseases and chronic inflammatory diseases, and as a preparation for inhibiting immune rejection at the time of transplantation.

This invention relates to anti-CD40 antibodies or antigen-binding fragments thereof that specifically recognize and weakly activate CD40 molecules in humans, cynomolgus monkeys, and mice, as well as immunoconjugates, pharmaceutical compositions, and combination products comprising said anti-CD40 antibodies or antigen-binding fragments thereof. The invention also relates to nucleic acids encoding said anti-CD40 antibodies or antigen-binding fragments thereof and host cells comprising said nucleic acids, and methods for preparing said anti-CD40 antibodies or antigen-binding fragments thereof. Furthermore, the invention relates to the use of said anti-CD40 antibodies or antigen-binding fragments thereof in the prevention or treatment of tumors or infectious diseases in subjects.

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.

The invention discloses a therapeutic target CD40 related to multiple myeloma bone diseases and application of a monoclonal antibody of the therapeutic target CD40. On one hand, it is found that formation and osteogenic differentiation of primary cilia of BMSCs can be effectively recovered by adding a CD40 neutralizing antibody into an MM-BMSCs co-culture system; on the other hand, the CD40 neutralizing antibody is found to reduce bone destruction and tumor load in a Vk * MYC myeloma mouse model. CD40 is expected to become a potential target spot for treating multiple myeloma bone diseases and has a very wide application prospect in the field of medical research.

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 relates to a biomarker for distinguishing between depression and bipolar disorder and uses thereof, elucidating a composition for distinguishing between depression and bipolar disorders and a method for providing information for distinguishing between depression and bipolar disorder, using same, wherein the composition is based on a biomarker composition comprising eotaxin, nerve growth factors (NGF), tumor necrosis factor-α (TNF-α), glial cell derived neurotrophic factor (GDNF), interleukin-1β (IL-1β), and serum soluble CD40 Ligand (sCD40L) within a serum sample and includes an agent for measuring the expression level of each of the six biomarker proteins.

Disclosed are an anti-CD40 antibody, an anti-PD-L1×CD40 bispecific antibody, and use thereof. The anti-CD40 antibody comprises a heavy chain variable region and a light chain variable region. The heavy chain variable region comprises the HCDR1, HCDR2 and HCDR3 in SEQ ID NO: 64. The light chain variable region comprises the LCDR1, LCDR2 and LCDR3 in SEQ ID NO: 65. The novel anti-CD40 agonistic antibody of the present invention can effectively regulate and control the activation of DC cells, has a stronger T cell activation effect while having low toxic and side effects, and is suitable for immunotherapy of tumors. The bispecific antibody of the present invention can maximize the anti-tumor drug effect, improve the selectivity of CD40 activation by means of PD-L1-dependent CD40 activation, and lower the toxic and side effects of the CD40 agonistic antibody.

The invention discloses a fusion protein linked with CD40-expressing cells containing APC and target specific T cells and application thereof, CD40L and other elements combined with CD40 are fused with target antigens specifically recognized by molecules in cells such as CAR-T or TCR-T to form a bifunctional protein, the DC maturation of the CD40L and other elements combined with CD40 can be enhanced, and meanwhile, the CD40L and other elements combined with CD40 can be combined with the target antigens specifically recognized by the molecules in the cells such as CAR-T or TCR-T to form the bifunctional protein, so that the CD40L and other elements combined with CD40 can be combined with the target antigens specifically recognized by the molecules in the cells. The target antigen is effectively delivered to the surface of the DC, so that the activation effect of the DC on cells such as CAR-T or TCR-T is enhanced, and particularly, the effect of enhancing the functions such as terminal amplification and reverse depletion of the cells such as CAR-T or TCR-T is remarkable.

Disclosed in the present invention are an antigen binding protein targeting CD40, and the preparation therefor and the use thereof. The antigen binding protein targeting CD40 has the characteristics of a high affinity to CD40 and a strong agonistic activity on signaling pathways, particularly the enhanced agonistic activity after crosslinking, so that the antigen binding protein targeting CD40 has a larger therapeutic window, and is expected to bring about new opportunities for the treatment of various tumors.

The invention provides a fusion protein and application thereof. The fusion protein comprises: at least three CD40L extracellular fragments; wherein the number of the CD40L extracellular segments is an integer larger than or equal to 3, and the C end and the N end of each CD40L extracellular segment are sequentially connected in series. The fusion protein disclosed by the invention can be combined with CD40, has strong activity of promoting the activation and proliferation of antigen presenting cells, further can effectively promote immune response and improve the anti-cancer capability of an autoimmune system, and has good clinical value and drug development value.

The invention provides biomarkers to predict effective treatment of cancer using an IAP antagonist. Identifying one or more of the identified biomarkers in a cancer patient allows a determination to be made whether the patient's cancer is likely to be successfully treated using an IAP antagonist. Accordingly, the invention relates generally to a companion diagnostic for IAP antagonist therapy. In particular, the biomarkers include IL-2Rα, IL-6r, CRP, EPO, CD27, CD40, TN-C, IL-18, PLGF, TNFrl and MCP-4.

There is an urgent need for an effective therapeutic vaccine against tuberculosis (TB), which remains a major public health problem. Current "classical" strategies under development have failed or are suboptimal, and more effective vaccines are needed to achieve the World Health Organization's 2035 End TB Strategy. We have generated a post-exposure / therapeutic TB vaccine candidate (CD40.TB) whose heavy chain consists of an antibody directed against a surface antigen (i.e., CD40) of antigen-presenting cells (i.e., dendritic cells) conjugated to three relevant Mycobacterium tuberculosis (Mtb) antigens and which is liable to induce potent anti-TB humoral and cellular immunity.

The present invention relates to modified myeloid cells or iPS or HSCs comprising a chimeric antigen receptor (CAR), or modified induced pluripotent stem cells (iPS) or hematopoietic stem cells (HSCs) comprising a CAR, the CAR comprising an extracellular antigen binding domain that binds to a tumor antigen or a tumor microenvironment (TME) antigen, a transmembrane domain, and a first intracellular signaling domain comprising the cytoplasmic tail of CD40 fused to a second intracellular signaling domain comprising the intracellular domain of CD3ζ. The present invention also relates to therapeutic uses thereof.

The present application relates to mesothelin-targeting CD40 agonistic multispecific antibody constructs for the treatment of solid tumors. Specifically, the present application relates to human agonistic CD40 multispecific antibody constructs for use in the treatment of solid tumors by engineering molecules that specifically target the CD40 pathway on tumor-associated APCs without the need for systemic CD40 activation.

Disclosed are an antigen-binding protein targeting PD-L1 and CD40, preparation therefor, and use thereof. The antigen-binding protein targeting PD-L1 and CD40, by means of blocking a PD-1 / PD-L1 inhibitory signaling pathway, acting on an activated CD40 receptor, and simultaneously activating an antigen-presenting cell and a lymphocyte, achieves a significant synergistic anti-tumor effect; meanwhile, the activation of the antigen-binding protein targeting PD-L1 and CD40 on an immune cell only occurs at a tumor microenvironment site, so that problems of systemic drug toxicity and side effects are significantly solved, which enables the antigen-binding protein targeting PD-L1 and CD40 to exert an excellent anti-tumor efficacy under very safe conditions.

The present invention discloses the application of CD40 antibody and LPS co-stimulated genetically modified B cells in the treatment of cancer, belonging to the field of biotechnology. First, the present invention discovers that B cells co-stimulated by LPS and anti-CD40 antibody can be used as cell vectors for gene therapy, continuously expressing dFv-LDP protein in vivo to treat cancer. The present invention discovers that B lymphocytes can continuously express dFv-LDP protein for a long time, solves the problem of too rapid reduction of the blood drug concentration of scFv protein to achieve a better therapeutic effect than directly injecting dFv-LDP protein, and at the same time can reduce the economic burden on patients caused by multiple injections of scFv protein.