B-cell maturation antigen

Last updated
TNFRSF17
Protein TNFRSF17 PDB 1oqd.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TNFRSF17 , BCM, BCMA, CD269, TNFRSF13A, tumor necrosis factor receptor superfamily member 17, TNF receptor superfamily member 17
External IDs OMIM: 109545 MGI: 1343050 HomoloGene: 920 GeneCards: TNFRSF17
Orthologs
SpeciesHumanMouse
Entrez

608

21935

Ensembl

ENSG00000048462

ENSMUSG00000022496

UniProt

Q02223

O88472

RefSeq (mRNA)

NM_001192

NM_011608

RefSeq (protein)

NP_001183

NP_035738

Location (UCSC) Chr 16: 11.97 – 11.97 Mb Chr 16: 11.13 – 11.14 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
BCMA TALL-1 binding domain
PDB 1oqd EBI.jpg
crystal structure of stall-1 and bcma
Identifiers
SymbolBCMA-Tall_bind
Pfam PF09257
InterPro IPR015337
SCOP2 1oqd / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

B-cell maturation antigen (BCMA or BCM), also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17), is a protein that in humans is encoded by the TNFRSF17 gene.

Contents

TNFRSF17 is a cell surface receptor of the TNF receptor superfamily which recognizes B-cell activating factor (BAFF). [5] [6] [7]

Serum B-cell maturation antigen (sBCMA) is the cleaved form of BCMA, found at low levels in the serum of normal patients and generally elevated in patients with multiple myeloma (MM). [8]

Function

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is preferentially expressed in mature B lymphocytes, and may be important for B cell development and autoimmune response. This receptor has been shown to specifically bind to the tumor necrosis factor (ligand) superfamily, member 13b (TNFSF13B/TALL-1/BAFF), and to lead to NF-kappaB and MAPK8/JNK activation. This receptor also binds to various TRAF family members, and thus may transduce signals for cell survival and proliferation. [7]

Interactions

TNFRSF17 has been shown to interact with the B-cell activating factor TNFSF13B. [9] [10] A conserved domain at the N-terminus, BCMA TALL-1 binding domain, is required for binding to the TNFSF13B. [9]

Clinical significance

TNFRSF17 is implicated in leukemia, lymphomas, and multiple myeloma [11] (see the "Mitelman Database" [12] and the Atlas of Genetics and Cytogenetics in Oncology and Haematology, [13] ).

As a drug target

An antibody-drug conjugate Belantamab mafodotin (GSK2857916) has evaluated in patients with relapsed/refractory multiple myeloma. [14] Belantamab mafodotin was approved in the United States in August 2020 for the treatment of patients with relapsed or refractory multiple myeloma who have received at least four prior therapies. [15]

Chimeric antigen receptor (CAR) T cells have emerged as an important therapy for multiple myeloma after first reports in preclinical and phase I clinical studies. [16] [17] A Phase 1b/2 study of JNJ-4528, a CAR-T cell therapy directed against BCMA in myeloma patients refractory to a proteasome inhibitor or immunomodulatory drug, and who had received an anti-CD38 antibody has been completed. [18]

ALLO-715 is a CAR-T therapy by Allogene Therapeutics that targets B-cell maturation antigen (BCMA). [19] As of June 2021, it is undergoing clinical trials for the treatment of multiple myeloma. [20] On 21 April 2021, the FDA granted Regenerative Medicine Advanced Therapy status to ALLO-715. [21] ALLO-715 is being investigated at Memorial Sloan Kettering Cancer Center and the Mayo Clinic [22] as part of the UNIVERSAL trial for multiple myeloma, on its own and in conjunction with the selective gamma secretase inhibitor nirogacestat. [20] [23]

Related Research Articles

<span class="mw-page-title-main">Multiple myeloma</span> Cancer of plasma cells

Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, kidney dysfunction, and infections may occur. Complications may include hypercalcemia and amyloidosis.

In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific antigen. The receptors are chimeric in that they combine both antigen-binding and T cell activating functions into a single receptor.

<span class="mw-page-title-main">CD30</span> Mammalian protein found in Homo sapiens

CD30, also known as TNFRSF8, is a cell membrane protein of the tumor necrosis factor receptor family and a tumor marker.

<span class="mw-page-title-main">CD40 (protein)</span> Mammalian protein found in Homo sapiens

Cluster of differentiation 40, CD40 is a type I transmembrane protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects.

<span class="mw-page-title-main">Bruton's tyrosine kinase</span> Kinase that plays a crucial role in B cell development.

Bruton's tyrosine kinase, also known as tyrosine-protein kinase BTK, is a tyrosine kinase that is encoded by the BTK gene in humans. BTK plays a crucial role in B cell development.

<span class="mw-page-title-main">Belimumab</span> Pharmaceutical drug

Belimumab, sold under the brand name Benlysta, is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS). It is approved in the United States and Canada, and the European Union to treat systemic lupus erythematosus and lupus nephritis.

<span class="mw-page-title-main">B-cell activating factor</span> Mammalian protein found in Homo sapiens

B-cell activating factor (BAFF) also known as tumor necrosis factor ligand superfamily member 13B and CD257 among other names, is a protein that in humans is encoded by the TNFSF13B gene. BAFF is also known as B Lymphocyte Stimulator (BLyS) and TNF- and APOL-related leukocyte expressed ligand (TALL-1) and the Dendritic cell-derived TNF-like molecule.

<span class="mw-page-title-main">CD137</span> Member of the tumor necrosis factor (TNF) receptor family

CD137, a member of the tumor necrosis factor (TNF) receptor family, is a type 1 transmembrane protein, expressed on surfaces of leukocytes and non-immune cells. Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), 4-1BB, and induced by lymphocyte activation (ILA). It is of interest to immunologists as a co-stimulatory immune checkpoint molecule, and as a potential target in cancer immunotherapy.

<span class="mw-page-title-main">APRIL (protein)</span> Protein-coding gene in the species Homo sapiens

A proliferation-inducing ligand (APRIL), also known as tumor necrosis factor ligand superfamily member 13 (TNFSF13), is a protein of the TNF superfamily recognized by the cell surface receptor TACI. It is encoded by the TNFSF13 gene.

<span class="mw-page-title-main">LIGHT (protein)</span> Secreted protein of the TNF superfamily

LIGHT, also known as tumor necrosis factor superfamily member 14 (TNFSF14), is a secreted protein of the TNF superfamily. It is recognized by herpesvirus entry mediator (HVEM), as well as decoy receptor 3.

<span class="mw-page-title-main">Transmembrane activator and CAML interactor</span> Protein-coding gene in the species Homo sapiens

Transmembrane activator and CAML interactor (TACI), also known as tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) is a protein that in humans is encoded by the TNFRSF13B gene.

<span class="mw-page-title-main">BAFF receptor</span> Mammalian protein found in Homo sapiens

BAFF receptor, also known as tumor necrosis factor receptor superfamily member 13C (TNFRSF13C) and BLyS receptor 3 (BR3), is a membrane protein of the TNF receptor superfamily which recognizes BAFF, an essential factor for B cell maturation and survival. In humans it is encoded by the TNFRSF13C gene.

<span class="mw-page-title-main">TNFSF12-TNFSF13</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor (ligand) superfamily, member 12-member 13, also known as TNFSF12-TNFSF13, is a human gene.

<span class="mw-page-title-main">Antibody–drug conjugate</span> Class of biopharmaceutical drugs

Antibody–drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 pharmaceutical companies were developing ADCs.

<span class="mw-page-title-main">TACI-CRD2 protein domain</span>

In molecular biology, TACI-CRD2 represents the second cysteine-rich protein domain found in the TACI family of proteins. Members of this family are predominantly found in tumour necrosis factor receptor superfamily, member 13b (TACI), and are required for binding to the ligands APRIL and BAFF. TACI-CRD2 stands for Transmembrane Activator and CAML Interactor- Cysteine Rich Domain 2.

<span class="mw-page-title-main">Serum B-cell maturation antigen</span> Cleaved form of B-cell maturation antigen

Serum B-cell maturation antigen (sBCMA) is the cleaved form of B-cell maturation antigen (BCMA), found at low levels in the serum of normal patients and generally elevated in patients with multiple myeloma (MM). Changes in sBCMA levels have been found to correlate with a MM patient’s clinical status in response to treatment.

Belantamab mafodotin, sold under the brand name Blenrep, is a medication for the treatment of relapsed and refractory multiple myeloma.

Idecabtagene vicleucel, sold under the brand name Abecma, is a cell-based gene therapy to treat multiple myeloma.

Ciltacabtagene autoleucel, sold under the brand name Carvykti, is an anti-cancer medication used to treat multiple myeloma. Ciltacabtagene autoleucel is a BCMA -directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose is customized using the recipient's own T-cells, which are collected and genetically modified, and infused back into the recipient.

Teclistamab, sold under the brand name Tecvayli, is a human bispecific monoclonal antibody used for the treatment of relapsed and refractory multiple myeloma. It is a bispecific antibody that targets the CD3 receptor expressed on the surface of T-cells and B-cell maturation antigen (BCMA), which is expressed on the surface of malignant multiple myeloma B-lineage cells.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000048462 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022496 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Laâbi Y, Gras MP, Carbonnel F, Brouet JC, Berger R, Larsen CJ, Tsapis A (November 1992). "A new gene, BCM, on chromosome 16 is fused to the interleukin 2 gene by a t(4;16)(q26;p13) translocation in a malignant T cell lymphoma". The EMBO Journal. 11 (11): 3897–3904. doi:10.1002/j.1460-2075.1992.tb05482.x. PMC   556899 . PMID   1396583.
  6. ↑ Laabi Y, Gras MP, Brouet JC, Berger R, Larsen CJ, Tsapis A (April 1994). "The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed". Nucleic Acids Research. 22 (7): 1147–1154. doi:10.1093/nar/22.7.1147. PMC   523635 . PMID   8165126.
  7. 1 2 "Entrez Gene: TNFRSF17 tumor necrosis factor receptor superfamily, member 17".
  8. ↑ Maglione PJ, Ko HM, Tokuyama M, Gyimesi G, Soof C, Li M, et al. (January 2020). "Serum B-Cell Maturation Antigen (BCMA) Levels Differentiate Primary Antibody Deficiencies". The Journal of Allergy and Clinical Immunology. In Practice. 8 (1): 283–291.e1. doi:10.1016/j.jaip.2019.08.012. PMC   6980522 . PMID   31430592.
  9. 1 2 Liu Y, Hong X, Kappler J, Jiang L, Zhang R, Xu L, et al. (May 2003). "Ligand-receptor binding revealed by the TNF family member TALL-1". Nature. 423 (6935): 49–56. Bibcode:2003Natur.423...49L. doi: 10.1038/nature01543 . PMID   12721620. S2CID   4373708.
  10. ↑ Shu HB, Johnson H (August 2000). "B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1". Proceedings of the National Academy of Sciences of the United States of America. 97 (16): 9156–9161. Bibcode:2000PNAS...97.9156S. doi: 10.1073/pnas.160213497 . PMC   16838 . PMID   10908663.
  11. ↑ "TNFRSF17 (tumor necrosis factor receptor superfamily, member 17)". atlasgeneticsoncology.org.
  12. ↑ "Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer". Archived from the original on 2016-05-25. Retrieved 2015-01-29.
  13. ↑ "Atlas of Genetics and Cytogenetics in Oncology and Haematology". atlasgeneticsoncology.org.
  14. ↑ Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. (February 2020). "Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study". The Lancet. Oncology. 21 (2): 207–221. doi:10.1016/s1470-2045(19)30788-0. PMID   31859245. S2CID   209425201.
  15. ↑ Baines AC, Ershler R, Kanapuru B, Xu Q, Shen G, Li L, et al. (November 2022). "FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma". Clinical Cancer Research. 28 (21): 4629–4633. doi:10.1158/1078-0432.CCR-22-0618. PMC   9633344 . PMID   35736811.
  16. ↑ Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, et al. (April 2013). "B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma". Clinical Cancer Research. 19 (8): 2048–2060. doi:10.1158/1078-0432.CCR-12-2422. PMC   3630268 . PMID   23344265.
  17. ↑ Ali SA, Shi V, Maric I, Wang M, Stroncek DF, Rose JJ, et al. (September 2016). "T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma". Blood. 128 (13): 1688–1700. doi:10.1182/blood-2016-04-711903. PMC   5043125 . PMID   27412889.
  18. ↑ Madduri D, Usmani SZ, Jagannath S, Singh I, Zudaire E, Yeh TM, et al. (2019-11-13). "Results from CARTITUDE-1: A Phase 1b/2 Study of JNJ-4528, a CAR-T Cell Therapy Directed Against B-Cell Maturation Antigen (BCMA), in Patients with Relapsed and/or Refractory Multiple Myeloma (R/R MM)". Blood. 134 (Supplement_1): 577. doi: 10.1182/blood-2019-121731 . ISSN   0006-4971. S2CID   209265279.
  19. ↑ Sommer C, Boldajipour B, Valton J, Galetto R, Bentley T, Sutton J, Ni Y, Leonard M, Van Blarcom T, Smith J, Chaparro-Riggers J (2018-11-29). "ALLO-715, an Allogeneic BCMA CAR T Therapy Possessing an Off-Switch for the Treatment of Multiple Myeloma". Blood. 132 (Supplement 1): 591. doi: 10.1182/blood-2018-99-119227 . ISSN   0006-4971.
  20. 1 2 Clinical trial number NCT04093596 for "Allogene Therapeutics" at ClinicalTrials.gov
  21. ↑ "FDA Grants RMAT Designation to ALLO-715 for Relapsed/Refractory Multiple Myeloma". OncLive. 21 April 2021. Retrieved 2022-05-10.
  22. ↑ "Safety and Efficacy of ALLO-715 and ALLO-647 BCMA Allogenic CAR T Cells in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL)". Mayo Clinic. Retrieved 2022-05-10.
  23. ↑ Taylor NP (2020-12-07). "ASH: Allogene's off-the-shelf CAR-T posts 60% response rate in fiercely competitive BCMA field". Fierce Biotech. Retrieved 2022-05-10.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article incorporates text from the public domain Pfam and InterPro: IPR015337
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