137 results about "CD40" patented technology

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 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.

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.

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.

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 invention provides a CD40 targeted medicine for realizing tumor immunodiagnosis and treatment by regulating PTPN1 / PTPN2 as well as a preparation method and application of the CD40 targeted medicine. The drug comprises a drug-loading membrane layer, perfluorinated compound PFC and glycerin are wrapped in the drug-loading membrane layer, the drug-loading membrane layer is coupled with a CD40 agonist, and the drug-loading membrane layer comprises phospholipid, cholesterol, a functionalized lipid polymer and AC484. The drug shows excellent biological stability and can be delivered to tumor tissue through a respiratory tract or a vein route; according to the medicine, accumulation and distribution of the medicine in the body are dynamically monitored through a 1H / 19F magnetic resonance imaging technology, noninvasive evaluation of the tumor state is achieved, immunotherapy is accurately guided, and therefore the tumor treatment effect is remarkably improved.

Provided herein are oncolytic viruses containing payload genes, including genes encoding IL-12, FLT3L, CD40 agonists, and / or CTLA-4 antibodies. Expression cassettes, pharmaceutical compositions, and methods of treatment using these viruses are also provided. Additionally, expression cassettes and CD40 agonist molecules are also provided in the present disclosure.

The present invention relates to combination therapies for treating cancer, optionally chemotherapy-resistant cancers, in a subject. The combination therapies comprise (a) an antibody or antigen-binding portion thereof that specifically binds to CD40, and (b) chemotherapy. The invention also relates to pharmaceutical compositions, kits and methods of using such therapies.

The invention provides a nucleic acid aptamer, and the nucleotide sequence of the nucleic acid aptamer is as shown in SEQ ID No: 1, or a sequence having 80% or more of identity with the nucleotide sequence. The nucleic acid aptamer successfully screened out in the invention has good affinity and specificity with CD40, and the binding capacity of the nucleic acid aptamer can be comparable with that of an antibody. In the functional level, the nucleic acid aptamer can be effectively combined with DC2.4 cells expressing CD40 and up-regulate the expression of related genes; the compound also shows remarkable immunostimulatory activity in an animal model, and shows a synergistic effect when being combined with an immunostimulant. The invention provides an important basis for subsequent development and transformation application of the CD40 nucleic acid aptamer, and also provides a new candidate tool and technical support for drug research and development based on a CD40 target spot.

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 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 a biomarker used as a diabetic neurogenic bladder (DNB) and a screening method and application thereof. Specifically, the invention provides a biomarker for the neurogenic bladder of diabetes, and the biomarker comprises one or more of ICAM2, VEGFA, JAML, PTPRJ, PTPRC, CD40, IL2RB and NCR1. By utilizing the biomarker provided by the invention, non-invasive and efficient identification of DNB can be realized, and a new molecular target is provided for complication prevention and control of diabetic patients.

The present invention relates to the field of pharmaceutical formulations, and provides a formulation of an anti-CD40L antibody and a preparation method for the formulation. More specifically, the present invention provides a formulation of a recombinant humanized anti-cluster of differentiation antigen CD40 ligand (CD40L) antibody and a preparation method for the formulation, and also relates to a use of the formulation in treating diseases or conditions related to inappropriate activation of a CD40L / CD40 mediated pathway.

The present disclosure provides antigen binding molecules that bind to CD40, such as bispecific antigen binding molecules that bind to two different epitopes of CD40. In some embodiments, the antigen binding molecules inhibit CD40L-induced activation and do not significantly agonize CD40 in the absence of CD40L. Also provided are methods for treating CD40 mediated diseases using the antigen binding molecules.

The application of the biomarker combination in the preparation of a drug for fulminant myocarditis belongs to the field of drugs. The application is characterized in that the biomarker combination comprises Siglec-5; the biomarker combination is further selected from the group consisting of sST2, PAI-1, Siglec-5, CD163, CD40, P-Cadherin, CD14, CTLA4. The application finds that the expression of the biomarker in the plasma of a patient with fulminant myocarditis is increased, and confirms the role of the biomarker as a drug target in relieving and / or improving fulminant myocarditis. The level of the biomarker can be controlled by a drug, the diagnosis and subsequent treatment of the disease can be more intensified, and the biomarker has great application value in clinical practice.

Provided in the present invention are a bispecific antibody that specifically binds to PD-L1 and CD40 and the use thereof. The bispecific antibody comprises: (1) a PD-L1-binding domain, which is VHH, wherein sequences of CDR1-3 in the VHH are as set forth in SEQ ID NOs: 2-4, respectively; and (2) a CD40-binding domain, comprising VH and VL, wherein sequences of HCDR1-3 in the VH are as set forth in SEQ ID NOs: 21-23, respectively, and sequences of LCDR1-3 in the VL are as set forth in SEQ ID NOs: 18-20, respectively.

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 present invention relates to a novel antagonistic anti-CD40 humanized antibody and, more specifically, to a novel humanized antibody specifically binding to CD40, which, by comprising a complementarity-determining region of a specific sequence, exhibits an excellent antagonistic effect by blocking CD40-CD40L signaling. The novel anti-CD40 humanized 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 suppressing immune rejection upon transplantation.

Provided herein are methods of treatment comprising administering oncolytic viruses comprising payload genes, such as genes encoding IL-12, FLT3L, CD40 agonists, and / or CTLA- 4 antibodies and antibodies to immunomodulatory agents.

The invention relates to a modified myeloid cell comprising a cytokine chimeric receptor (CCR), wherein said CCR comprises an extracellular domain comprising an extracellular domain of a cytokine receptor which binds soluble molecules present in the tumor microenvironment (TME); a transmembrane domain; and an intracellular signaling domain comprising CD40 cytotail, CD3zeta intracellular domain and / or STING or one of its fragments. The invention also relates to a modified cell comprising a CCR and a transgene coding for a cytokine. The invention also relates to therapeutic uses thereof and to methods and pharmaceutical compositions for the treatment of cancer.

The invention relates to a pharmaceutical composition of FAP / CD40 binding molecules and medical application thereof. In particular, a pharmaceutical composition comprises a FAP / CD40 binding molecule and a buffering agent. The pharmaceutical composition has good biological activity and stability.

The present invention provides immunostimulatory nucleic acids that have an affinity to a specific target protein. The present invention also provides templates and methods for making and using the immunostimulatory nucleic acids. Further, methods for linking the immunostimulatory nucleic acids to antigens and using the resulting complexes to enhance an immune response are provided.

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

Provided is a recombinant fusion protein comprising (a) an anti-CD40 antibody or antigen-binding fragment thereof comprising a heavy chain variable region and a light chain variable region, and (b) a CD47 binding domain. Nucleic acid molecules encoding the recombinant fusion proteins, vectors comprising the nucleic acid molecules, and host cells transformed or transfected with the vectors or nucleic acid molecules are provided. In addition, the invention also provides a production method of the recombinant fusion protein, medical application of the recombinant fusion protein and a kit containing the recombinant fusion protein.