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

The invention discloses a neutralizing nucleic acid aptamer for targeted inhibition of a B cell activating factor and application of the neutralizing nucleic acid aptamer in treatment of systemic lupus erythematosus. The neutralizing aptamer disclosed by the invention can be used for efficiently inhibiting the combination of BAFF and specific receptors on a B cell membrane, including a BAFF receptor (BAFF-R), a human calcium regulatory cyclophilin ligand interaction molecule (TACI) and a B cell maturation antigen (BCMA), so that the proportion of plasma cells, plasma mother cells and hair growth center B cells is reduced, and finally, the generation and secretion of autoantibodies are reduced; the compound has a targeted therapeutic effect on systemic lupus erythematosus. Compared with an existing biological agent for neutralizing BAFF, the neutralizing nucleic acid aptamer has the advantages of being high in specificity, high in affinity, easy to synthesize, low in immunogenicity, low in cost, capable of being designed and programmed and the like, is a potential novel nucleic acid preparation for SLE targeted therapy, and has a good clinical transformation application prospect.

The disclosure concerns a method of treating cancer, especially, such as multiple myeloma, involving the combination of an anti-BCMA (B cell maturation antigen) antibody, Belantamab mafodotin -GSK2857916- and a gamma-secretase inhibitor, e.g., nirogacestat -PF03084014-. The disclosure also relates to dosages, duration of treatment and time lapses between administration of the anti-BCMA antibody and the gamma-secretase inhibitor.

The present disclosure provides chimeric antigen receptor (CAR) molecule specific for B cell maturation antigen (BC-MA), compositions and methods for treating immune-related disorders, specifically, plasma cell pathologies such as multiple myeloma (MM).

Antibodies and antigen-binding fragments thereof that bind to B cell maturation antigen (BCMA), and methods of using the same are provided.

A B cell maturation antigen (BCMA) is expressed on plasma cells. The present invention provides methods of desensitizing a patient in need of solid organ transplantation against HLA antibodies using bispecific antibodies that bind to both BCMA and CD3 and activate T cells by the CD3 complex in the presence of plasma cells expressing BCMA. In certain embodiments, the bispecific antibodies of the invention reduce alloantibody levels and / or reduce computational population reactive antibody levels to promote solid organ transplantation and / or improve long term graft survival and / or function.

The present disclosure belongs to the fields of biotechnology and biological medicine, and specifically relates to an antibody targeting a B cell maturation antigen (BCMA) and related products thereof and medical applications. Specifically, the antibody contains a variable light chain and a variable heavy chain. The variable light chain contains a light chain complementarity-determining region (CDR) 1, a light chain CDR2, and a light chain CDR3. The light chain CDR1 has a sequence as shown in SEQ ID NO. 1, the light chain CDR2 has an amino acid sequence as shown in SEQ ID NO. 2, and the light chain CDR3 is as shown in SEQ ID NO. 3 or SEQ ID NO. 4.

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. Also disclosed is 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.

This provides a multispecific antibody that binds to BCMA. [Solution] A multispecific human heavy chain antibody (e.g., UniAb) that binds to B cell maturation antigen (BCMA). TM Disclosed are methods for producing such antibodies, compositions comprising pharmaceutical compositions containing such antibodies, and their use for treating disorders characterized by BCMA expression. In one embodiment, a multispecific antibody that binds to BCMA is provided, comprising a first binding unit comprising a variable region comprising a CDR3 sequence having at least 85% sequence identity with a specific sequence.

The present disclosure relates to compositions and methods for treating diseases using chimeric antigen recipient cells and / or antigen binding domains that target BCMA.

The present disclosure provides methods of treating a disease or disorder responsive to inhibition or blocking of B cell maturation antigen (BCMA) by administering one or more BCMA antagonists.

This invention relates to GPRC5D and BCMA-specific chimeric antigen receptors (CARs), specifically providing CARs containing an extracellular antigen-binding domain that binds to a G protein-coupled receptor class C5 group D member (GPRC5D) and B cell maturation antigen (BCMA). The invention also relates to genetically engineered cells expressing such CARs and their use in adoptive cell therapy.

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 are disclosed. Further disclosed are pharmaceutical compositions, screening and medical treatment methods.

Disclosed is a nucleic acid encoding a chimeric antigen receptor comprising an extracellular domain, a transmembrane domain, and an intracellular domain comprising a signal transduction domain, the extracellular domain comprising an antigen recognition domain, the antigen recognition structural domain is composed of a fully human single variable heavy (VH) structural domain combined with a first epitope of a B cell maturation antigen (BCMA).

Compositions and methods described herein relate to chimeric antigen receptors (CARs) targeting B cell maturation antigen (BCMA) and uses thereof in therapy. Engineered T cells comprising an anti-BCMA CAR are also provided. The engineered cells may comprise a genetic modification in one or more of the HLA-A, HLA-B, TRAC, CIITA, or TGFBR2 genes.

The present disclosure provides compositions and methods for inhibiting or preventing an immune response to an immunogen (e.g., an immunogenic delivery vehicle) in a subject in need thereof, comprising administering to the subject an effective amount of a plasma cell depleting agent, e.g., an antigen-binding molecule that binds to B cell maturation antigen (BCMA) and cluster of differentiation 3 (CD3) (e.g., an anti-BCMA×CD3 bispecific antibody, or a functional fragment thereof) or a B cell depleting agent, e.g., an antigen-binding molecule that binds to CD20 and CD3 (e.g., an anti-CD20×CD3 bispecific antibody, or a functional fragment thereof), either alone or in combination with one another, and / or in combination with an immunoglobulin depleting agent such as a neonatal fragment crystallizable (Fc) receptor (FcRn) blocker (e.g., efgartigimod).

Genetically engineered immune cells (e.g., T cells or NK cells) expressing anti-BCMA, anti-TACI, or anti-BCMA / anti-TACI chimeric antigen receptors and their use in cancer therapy. In some embodiments, the genetically engineered immune cell may be an armored CAR-T or CAR-NK cell, which further expresses an armored polypeptide for enhancing the characteristic of the CAR-T or CAR-NK cell.

The present invention relates to an isolated monoclonal antibody targeting B cell maturation antigen (BCMA), wherein the antibody binds to both human BCMA and monkey BCMA. The present invention also relates to a nucleic acid encoding the antibody, a method for producing the monoclonal antibody, and a pharmaceutical composition comprising the antibody of the present invention.

A gene using a BCMA extracellular domain as a marker, a polypeptide, a recombinant expression vector, a genetically engineered cell, and use thereof are provided. The gene tBCMA is a gene encoding a complete or partial sequence of the BCMA extracellular domain, or a gene encoding a sequence at least 85% identical to the complete or partial sequence. An extracellular domain polypeptide (tBCMA) of the B cell maturation antigen is used as a marker for the technology of detecting and removing the genetically engineered immune cells. The gene using the BCMA extracellular domain as the marker can be widely used for the detection of various genetically engineered immune cells, thereby effectively solving the problems of detection of the genetically engineered immune cells after preparation and infusion, and providing a feasible strategy when these cells need to be removed due to serious toxic and side effects in clinical therapy.

The application discloses a neutralizing nucleic acid aptamer capable of specifically combining with human APRIL and application thereof in inhibiting antibody secretion. The neutralizing nucleic acid aptamer of the application can efficiently neutralize extracellular APRIL molecules in vitro and in vivo, thereby blocking the combination of the molecules with a human calcium-binding cyclophilin ligand-interacting molecule (TACI) and a B cell maturation antigen (BCMA) on a B cell membrane, and finally inhibiting the generation and secretion of antibodies. Compared with the existing biological preparation atacicept for targeting and neutralizing APRIL, the APRIL neutralizing nucleic acid aptamer involved in the application has the advantages of high specificity, high affinity, low immunogenicity and low cost, is a novel nucleic acid drug preparation for inhibiting antibody secretion, and has a great clinical application prospect.

The present disclosure is based at least in part on the discovery of novel BCMA antibodies or antigen-binding fragments thereof, and generally, genetically modified cells (e.g., iNKT cells, CAR T cells, etc.) expressing chimeric antigen receptors comprising anti-BCMA antibodies or antigen-binding fragments thereof exhibit improved properties, including increased binding to BCMA, killing of BCMA-expressing cancer cells in vitro and in vivo, and enhanced persistence in treated subjects.

To provide compositions and methods that can be used in methods to treat multiple myeloma.SOLUTION: The invention provides an isolated or 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.SELECTED DRAWING: None

The present disclosure is based, at least in part, on the discovery of novel BCMA antibodies or antigen-binding fragments thereof, and genetically modified cells (e.g., iNKT cells, CAR T cells, etc.) expressing chimeric antigen receptors comprising anti-BCMA antibodies or antigen-binding fragments thereof exhibit improved properties, including increased binding to BCMA, in vitro and in vivo killing of cancer cells expressing BCMA; and enhanced persistence in a subject receiving therapy.

The present disclosure relates to a novel class of BCMA (B cell maturation antigen, TNFRSF17) binding molecules, in particular to anti-BCMA antibodies and other BCMA binding molecules, and antigen binding fragments. The present invention further relates to recombinant molecules comprising said BCMA binding molecules, such as, chimeric antigen receptors (CARs), BiTEs and ADCs. Another object of the present invention is an engineered immune cell, suitably, a T cell comprising said CAR. Uses thereof in therapeutic methods of said BCMA binding molecule, said recombinant molecule and said engineered immune cell are further described.

There is provided a method of treating an autoimmune disease comprising administering to a patient a cell composition made by transducing cells with a mixture of vectors, the mixture comprising: (i) a first vector which expresses a first chimeric antigen receptor (CAR) which binds CD19; and (ii) a second vector which expresses a second CAR which binds B cell maturation antigen (BCMA). There is also provided a method for selectively deleting anti-BCMA CAR-expressing cells and a method for restoring the plasma cell compartment in a patient who has received such a treatment.

Compositions and methods of treatment that can be used in the treatment of multiple myeloma are provided. The present invention provides an isolated or purified nucleic acid sequence encoding a chimeric antigen receptor (CAR), the CAR comprising an antigen recognition portion and a T cell activation portion, the antigen recognition portion being directed against B cell maturation antigen (BCMA), and a host cell, such as a T cell or a natural killer (NK) cell, that expresses the CAR.

The present disclosure provides compositions and methods for inhibiting or preventing an immune response to an immunogen (e.g., an immunogenic delivery vehicle) in a subject in need thereof, comprising administering to the subject an effective amount of a plasma cell depleting agent, e.g., an antigen-binding molecule that binds to B cell maturation antigen (BCMA) and cluster of differentiation 3 (CD3) (e.g., an anti-BCMAxCD3 bispecific antibody, or a functional fragment thereof) or a B cell depleting agent, e.g., an antigen-binding molecule that binds to CD20 and CD3 (e.g., an anti-CD20xCD3 bispecific antibody, or a functional fragment thereof), either alone or in combination with one another, and / or in combination with an immunoglobulin depleting agent such as a neonatal fragment crystallizable (Fc) receptor (FcRn) blocker (e.g., efgartigimod).

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.

A chimeric antigen receptor (CAR) is provided that contains an extracellular antigen binding domain that binds to a G protein coupled receptor class C Group 5 D member (GPRC5D) and a B cell maturation antigen (BCMA). The disclosure also relates to genetically engineered cells expressing such CARs and their use in adoptive cell therapy.

This disclosure provides a method for treating a subject with cancer or light chain amyloidosis, the method comprising administering to the subject a combination therapy containing an effective amount of nirostat dihydrobromide form A and B cell maturation antigen (BCMA) targeted therapy and providing the use of the combination therapy.

The present invention relates to novel humanized antibodies that bind to the B cell maturation antigen (BCMA), and to immunostimulatory antigen binding molecules comprising these BCMA antibodies, in particular to antigen binding molecules comprising a 4-1BBL trimer that target BCMA; processes for their production; and their use in the treatment of cancer.