50 results about "B-Cell Maturation Antigen" patented technology

The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

The disclosure relates to B-cell maturation antigen (BCMA), a receptor for APRIL and BAFF, and its use as an immunoregulatory agent in treatment of immunological disorders such as multiple sclerosis. The disclosure provides methods and compositions for treating neurodegenerative immunological disorders in mammals by administering soluble BCMA, an antibody against BCMA, or an antibody against a BCMA ligand, e.g., APRIL or BAFF.

The invention provides a BCMA-based (B cell maturation antigen-based) chimeric antigen receptor, comprising following cis-form cascade domains: CD8a leader region, scFv fragment BCMA scFv of anti-BCMA antibody, CD8a hinge region and transmembrane region, CD28 intracellular signal domain and CD3 Zeta intracellular signal domain; the CD3 Zeta intracellular signal domain is wild CD3 Zetaintracellular signal domain or mutant CD3 Zeta mut intracellular signal domain; the BCMA-based chimeric antigen receptor can enhance anti-apoptotic capability of T-cells and enhance CAR T-cell and antigen bonding and signal conduction; T-cells with the BCMA-based chimeric antigen receptor show good tumor targeting performance in in-vivo experiments, tumors diminish significantly after two weeks of dosage, and the T-cells have excellent therapeutic effect in vivo.

The present invention concerns antigen binding proteins and fragments thereof which specifically bind B Cell Maturation Antigen (BCMA), particularly human BCMA (hBCMA) and which inhibit the binding of BAFF and APRIL to the BCMA receptor. Further disclosed are pharmaceutical compositions, screening and medical treatment methods.

The invention relates to a chimeric antigen acceptor of a target BCMA (B cell maturation antigen). The chimeric antigen acceptor comprises an extracellular identification region, a hinge region, a transmembrane region and an intracellular signal region, wherein the extracellular identification region has a BCMA resisting nanometer antibody sequence, and the BCMA resisting nanometer antibody sequence is a heavy-chain variable region sequence combining with BCMA and from alpacas. More specifically, the BCMA resisting nanometer antibody sequence is BCMA monoclonal antibody B1 or B65, the amino acid sequence of the B1 is as shown in SEQID NO.1, and the amino acid sequence of the B65 is as shown in SEQID NO.2. According to the chimeric antigen acceptor disclosed by the invention, compared witha traditional mouse-derived SCFV or humanized SCFV, the nanometer antibody from the alpacas is used, and has small molecule quantity and immunogenicity, the possibility that CAR-T cells prepared on the base of the nanometer antibody produce HAMA effects in vivo is smaller, the remaining time of the CAR-T cells in vivo can be longer, the CAR-T cells pass through BCMA protein on the surfaces of target tumor cells and activate signal channels at the downstream part of T cells, the capacity for killing tumor cells having BCMA target points is given to the T cells, and BCMA positive blood tumor canbe efficiently and specifically treated.

The invention relates to a chimeric antigen receptor (CAR) and application thereof. The CAR comprises BCMA (B-cell maturation antigen) binding structural domains, transmembrane structural domains, oneor a plurality of co-simulation structural domains and intracellular signal transduction structural domains. The BCMA binding structural domains comprise heavy chain complementary determining regionsHCDR 1-3, and amino acid sequences of the HCDR 1-3 are sequentially shown as SEQ ID NO:1-3.

The invention relates to a fully human anti-BCMA (B Cell Maturation Antigen) chimeric antigen receptor and application thereof. The chimeric antigen receptor comprises an extracellular domain, a membrane spanning domain and at least one intracellular domain capable of binding antigens, wherein the extracellular domain is an anti-BCMA single domain antibody; and the fully human anti-BCMA antibody comprises a heavy chain variable region and a light chain variable region having specific sequences. The chimeric antigen receptor disclosed by the invention has low immunogenicity, small rejection reaction and high safety, the solid tumor foci can be effectively reduced, and the tumor treatment effect is effectively improved.

The present invention provides a chimeric antigen receptor (CAR) comprising: (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

The present invention relates to chimeric antigen receptor targeting BCMA(J22.9), and uses thereof, and particularly provides a polynucleotide sequence, which is selected from (1) a polynucleotide sequence containing the coding sequence of an anti-BCMA single chain antibody, the coding sequence of a human CD8 alpha hinge region, the coding sequence of a human CD8 transmembrane region, and the coding sequence of a human 41BB intracellular region, wherein the coding sequences are sequentially linked, and (2) a sequence complementary to the polynucleotide sequence (1). The present invention further provides a related fusion protein, a vector containing the coding sequence, and uses of the fusion protein, the coding sequences, and the vector.

Polypeptides and proteins that specifically bind to and immunologically recognize B-Cell Maturation Antigen (BCMA) are disclosed. Chimeric antigen receptors (CARs), anti-BCMA binding moieties, nucleic acids, recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, and conjugates relating to the polypeptides and proteins are also disclosed. Methods of detecting the presence of cancer and methods of treating or preventing cancer are also disclosed.

The invention relates to a chimeric antigen receptor targeting a novel BCMA (B-cell maturation antigen) and application thereof. Specifically, the invention provides a polynucleotide sequence, which is chosen from: (1) a polynucleotide sequence of polynucleotide codding sequences containing the codding sequence of the anti-BCMA single-chain antibody, the coding sequence of the human CD8Alpha hingeregion, the coding sequence of the human CD8 transmembrane region, the coding sequence of the human 41BB intracellular region, the coding sequence of the human CD3Zeta intracellular region and the coding sequence of the mbIL15 structure connected in sequence; and (2) complementary sequences of the polynucleotide sequences (1). The invention further provides a related fusion protein, a vector containing the coding sequence and application of the fusion protein, the coding sequence and the vector.

The invention belongs to the technical field of genetic engineering, and specifically relates to an anti-BCMA (B-cell Maturation Antigen) humanized single-chain antibody and application thereof. The amino acid sequence of the anti-BCMA humanized single-chain antibody is as show in SEQ ID NO: 19 or 20 or 21 or 22 or 23. The anti-BCMA humanized single-chain antibody is formed by sequentially connecting a light chain variable region, a Linker and a heavy chain variable region; the humanization degree is high; the immunogenicity of CAR (Chimeric Antigen Receptor) can be effectively reduced; the continuity and safety of CAR-T (Chimeric Antigen Receptor T-cell) in vivo can be enhanced.

The present invention provides a bi-specific molecule which comprises: (i) a first domain which binds B cell maturation antigen (BCMA) and comprises at least part of a proliferation-inducing ligand (APRIL); and (ii) a second domain capable of activating a T cell. The invention also provides the use of such a molecule in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

The present invention provides a chimeric antigen receptor (CAR) comprising: (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.

A bispecific bi- or trivalent antibody specifically binding to the two targets which are extracellular domain of human B cell maturation antigen (BCMA) and human CD3ε, wherein the variable domains VL and VH in a light chain and the respective heavy chain are replaced by each other, characterized in comprising a constant domain CL wherein the amino acid at position 124 is substituted independently by lysine (K), arginine (R) or histidine (H) (numbering according to Kabat), and in the respective constant domain CH1 the amino acid at position 147 and the amino acid at position 213 is substituted independently by glutamic acid (E), or aspartic acid (D) (numbering according to EU index of Kabat). Also the manufacture and use of said antibody.

Disclosed herein are B cell maturation antigen binding proteins with improved binding affinities and improved ability to mediate killing of cancer cells expressing B cell maturation antigen (BCMA). Pharmaceutical compositions comprising the binding proteins disclosed herein and methods of treatment of a cancer or a metastasis thereof using such formulations are further provided.

The presently disclosed subject matter provides for methods and compositions for treating multiple myeloma. It relates to chimeric antigen receptors (CARs) that specifically target B cell maturation antigen (BMCA), and immunoresponsive cells comprising such CARs. The presently disclosed BMCA-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

The presently disclosed subject matter provides for methods and compositions for treating multiple myeloma. It relates to chimeric antigen receptors (CARs) that specifically target B cell maturation antigen (BMCA), and immunoresponsive cells comprising such CARs. The presently disclosed BMCA-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

The invention relates to a bispecific antibody specifically binding to human B cell maturation antigen (BCMA) and to human CD3ϵ (CD3) together with an immunotherapeutic drug for combined use in treating multiple myeloma.

Described herein are methods for producing and utilizing T cells comprising chimeric antigen receptors (CAR) comprising two or more extracellular domains, each comprising a portion of the extracellular domain of a Tumor Necrosis Factor (TNF) superfamily receptor ligand, e.g., A PRoliferation-Inducing Ligand (APRIL). The CARs described herein are capable of targeting, e.g., B cell maturation antigen (BCMA) and / or transmembrane activator and CAML interactor (TACI). Additionally, the CAR T cells of the present invention overcome resistance to anti-BCMA targeted therapies and utilize dimerizing and trimerizing transmembrane domains for optimal function. Further, the invention is related to methods of treating cancer (e.g., multiple myeloma (MM)), plasma cell diseases or disorders, autoimmunediseases or disorders, or transplant rejection.

Disclosed herein are B cell maturation antigen binding proteins with improved binding affinities and improved ability to mediate killing of cancer cells expressing B cell maturation antigen (BCMA). Pharmaceutical compositions comprising the binding proteins disclosed herein and methods of treatment of a cancer or a metastasis thereof using such formulations are further provided.

The invention provides a nano antibody for resisting a B cell maturation antigen and an application of the nano antibody. A heavy chain variable region of the nano antibody for resisting the B cell maturation antigen comprises a complementary determining region 1 as shown in SEQ ID NO. 1, a complementary determining region 2 as shown in SEQ ID NO. 2 and a complementary determining region 3 as shown in SEQ ID NO. 3. The antibody screened by using a phage display nano antibody library has a specific CDR region, and the obtained antibody can be specifically bound with a BCMA antigen and has good affinity; When being used as an antigen binding structural domain to construct a chimeric antigen receptor and a CAR-T cell, the antibody has obvious killing activity on BCMA positive tumor cells. Therefore, the nano antibody has a wide application prospect in the aspect of immunotherapy of multiple myeloma.

The invention provides a nano-antibody for resisting a B cell maturation antigen and application of the nano-antibody. The nano-antibody for resisting the B cell maturation antigen is BCMA-12, and a heavy chain variable region of the BCMA-12 comprises a complementary determining region 1 as shown in SEQ ID NO. 1, a complementary determining region 2 as shown in SEQ ID NO. 2 and a complementary determining region 3 as shown in SEQ ID NO. 3. The nano-antibody screened by using a phage display nano-antibody library has a specific CDR region, and the obtained nano-antibody can specifically bind to a BCMA antigen and has good affinity; when being used as an antigen binding structural domain to construct a chimeric antigen receptor and a CAR-T cell, the nano-antibody has obvious killing activity on BCMA-positive tumor cells; and therefore, the nano-antibody has wide application prospects in the aspect of immunotherapy of multiple myeloma.

The invention provides an antibody for resisting a B cell maturation antigen and application of the antibody. The antibody is BCMA-21, and a heavy chain variable region of the antibody comprises a complementary determining region 1 as shown in SEQ ID NO. 1, a complementary determining region 2 as shown in SEQ ID NO. 2 and a complementary determining region 3 as shown in SEQ ID NO. 3. The antibody screened by utilizing a phage display nano antibody library has a specific CDR region, can specifically bind to a BCMA antigen with good affinity, and has Ka (1 / Ms) of 7.48E+06, Kd (1 / s) of 8.50E-04, and KD (M) of 1.14E-10. A chimeric antigen receptor and CAR-T cell can be constructed by using the antibody as the antigen-binding domain, and have obvious killing activity on BCMA-positive tumor cells.

The invention relates to an isolated chimeric antigen receptor polypeptide (CAR), wherein the CAR comprises an extracellular antigen-binding domain, comprising an antibody or antibody fragment that binds a B Cell Maturation Antigen (BCMA) polypeptide. The CAR preferably binds an epitope comprising one or more amino acids of residues 13 to 32 of the N-terminus of human BCMA. The invention further relates to a nucleic acid molecule encoding the CAR of the invention, a genetically modified immune cell, preferably a T cell, expressing the CAR of the invention and the use of said cell in the treatment of a medical disorder associated with the presence of pathogenic B cells, such as a disease of plasma cells, memory B cells and / or mature B cells, in particular multiple myeloma, non-Hodgkin's lymphoma or autoantibody-dependent autoimmune diseases.

The invention relates to a target BCMA chimeric antigen receptor, a nucleic acid sequence, a carrier and an application, and a composition and a method for treating cancers using CAR cells. The composition comprises the isolated nucleic acid sequence for coding a CAR, wherein the CAR comprises an extracellular structure domain, a transmembrane structure domain and an intracellular structure domain; the extracellular structure domain is bound with a BCMA; the isolated nucleic acid sequence includes the nucleic acid sequence as shown in SEQ ID NO: 1, 2 or 9; the intracellular structure domain comprises a co-stimulation signal conduction region; and the co-stimulation signal conduction region comprises molecules selected from CD27, CD28, 4-1BB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-related antigen-1(LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3 and any combination thereof.

The invention provides a monoclonal antibody for resisting a B cell maturation antigen and an application of the monoclonal antibody. A heavy chain variable region of the monoclonal antibody for resisting the B cell maturation antigen comprises a complementary determining region 1 as shown in SEQ ID NO. 1, a complementary determining region 2 as shown in SEQ ID NO. 2 and a complementary determining region 3 as shown in SEQ ID NO. 3. The antibody screened by using a phage display nano-antibody library has a specific CDR region, the obtained antibody can be specifically bound with a BCMA antigen, the affinity is good, the Ka(1 / Ms) is 3.03E+06, the Kd(1 / s) is 2.14E-04, and the KD(M) is 7.09E-11. Therefore, the monoclonal antibody has a wide application prospect in the aspect of immunotherapy of multiple myeloma.