The Role of B-Cell Maturation Antigen in the Biology and Management of, and as a Potential Therapeutic Target in, Multiple Myeloma

@article{Sanchez2017TheRO,
  title={The Role of B-Cell Maturation Antigen in the Biology and Management of, and as a Potential Therapeutic Target in, Multiple Myeloma},
  author={Eric Sanchez and Emily J. Smith and Moryel A. Yashar and Saurabh Patil and Mingjie Li and Autumn L. Porter and Edward J. Tanenbaum and Remy E. Schlossberg and Camilia M. Soof and Tara Hekmati and George Y Tang and Cathy S. Wang and Haiming Chen and James R. Berenson},
  journal={Targeted Oncology},
  year={2017},
  volume={13},
  pages={39-47}
}
B-cell maturation antigen (BCMA) was originally identified as a cell membrane receptor, expressed exclusively on late stage B-cells and plasma cells (PCs). Investigations of BCMA as a target for therapeutic intervention in multiple myeloma (MM) were initiated in 2007, using cSG1 as a naked antibody (Ab) as well as an Ab–drug conjugate (ADC) targeting BCMA, ultimately leading to ongoing clinical studies for previously treated MM patients. Since then, multiple companies have developed anti-BCMA… Expand
17 Citations
Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy
TLDR
Preclinical and clinical data of current BCMA-targeted immunotherapies with various mechanisms of action are highlighted and crucial studies will enhance selective anti-MM response, transform the treatment paradigm, and extend disease-free survival in MM. Expand
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TLDR
Clinical data outline the potential for BCMA-targeted therapies to improve the treatment landscape for MM and suggest that these therapies may hold promise for deep and durable responses and support further investigation in earlier lines of treatment, including newly diagnosed MM. Expand
Transmembrane Activator and CAML Interactor (TACI): Another Potential Target for Immunotherapy of Multiple Myeloma?
TLDR
The biology of TACI is reviewed, focusing on its role in normal B and plasma cells and malignant MM cells, and various ways to incorporate TACi as a potential target for immunotherapies against MM are discussed. Expand
T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma.
TLDR
CAR-BCMA T cells had substantial activity against heavily treated relapsed/refractory MM and should encourage additional development of CAR T-cell therapies for MM. Expand
Rethinking mechanisms of neurotoxicity with BCMA directed therapy.
TLDR
A review of the literature in this field highlights the possibility of on-target toxicities due to neural expression of BCMA and draws attention to the need for further investigation of these toxicities. Expand
Analysis of the receptor BCMA as a biomarker in systemic lupus erythematosus patients
TLDR
The receptor sBCMA could be a potential biomarker of disease activity in SLE patients andSoluble levels of the receptor s BCMA and its ligands sAPRIL and sBAFF were increased in Sle patients compared with HCs, and correlated strongly with disease activity. Expand
Selective targeting of multiple myeloma by B cell maturation antigen (BCMA)-specific central memory CD8+ cytotoxic T lymphocytes: immunotherapeutic application in vaccination and adoptive immunotherapy
TLDR
The identification of novel engineered peptides specific to BCMA, BCMA72-80 (YLMFLLRKI), and BCMA54-62 (YILWTCLGL), which display improved affinity/stability to HLA-A2 compared to their native peptides and induce highly functional BCMA-specific CTL that mediate effective and long-lasting immunity against MM are reported. Expand
Therapeutic effect of dual CAR-T targeting PDL1 and MUC16 antigens on ovarian cancer cells in mice
TLDR
Dual CAR-T cells were shown to be two to four times more efficacious than single CAR- t cells in terms of survival time and PD1-antiMUC16 CAR-t cells showed more potent antitumor activity than singleCAR-T cell in vivo. Expand
An Anti-BCMA RNA Aptamer for miRNA Intracellular Delivery
TLDR
The generation of the first-ever-described nuclease resistant RNA aptamer selectively binding to B cell maturation antigen and conjugated to microRNA-137 and anti-miR-222, demonstrating high potential against tumor cells is described. Expand
Normalization of serum B‐cell maturation antigen levels predicts overall survival among multiple myeloma patients starting treatment
TLDR
It is found that among multiple myeloma patients starting a new treatment, those who begin treatment within normal sBCMA limits have improved progression‐free survival (PFS) and overall survival (OS) than those who do not and normalization of s BCMA may be an accurate predictor of OS for MM patients during treatment. Expand
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References

SHOWING 1-10 OF 54 REFERENCES
Antibody targeting of B-cell maturation antigen on malignant plasma cells
TLDR
B-cell maturation antigen (BCMA) antibodies show cytotoxic activity both as naked IgG and as drug conjugates and warrant further evaluation as therapeutic candidates for plasma cell malignancies. Expand
An anti-B cell maturation antigen bispecific antibody for multiple myeloma.
TLDR
A bispecific antibody against B cell maturation antigen (BiFab-BCMA) is reported, which potently and specifically redirects T cells to lyse malignant multiple myeloma cells. Expand
Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival.
TLDR
Evidence that B-lymphocyte stimulator (BLyS) can modulate the proliferative capacity and survival of MM cells is provided and evidence that BLyS is expressed by MM cells and is present in the bone marrow of patients with MM. Expand
B-cell Maturation Antigen Is a Promising Target for Adoptive T-cell Therapy of Multiple Myeloma
TLDR
This work designed and tested the first anti-BCMA CARs to be reported and transduced T cells with lentiviral vectors encoding these CARs that exhibited BCMA-specific functions including cytokine production, proliferation, cytotoxicity, and in vivo tumor eradication. Expand
A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo
TLDR
Results show that BI 836909 is a highly potent and efficacious approach to selectively deplete BCMA-positive MM cells and represents a novel immunotherapeutic for the treatment of MM. Expand
Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment.
TLDR
An IgG-based BCMA-T cell bispecific antibody (EM801) was constructed and showed that it increased CD3+ T-cell/myeloma cell crosslinking, followed by CD4+/CD8+ T cell activation, and secretion of interferon-γ, granzyme B, and perforin, which is CD4 and CD8 T  cell mediated. Expand
Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma.
TLDR
It is demonstrated that GSK2857916 has potent and selective anti-MM activities via multiple cytotoxic mechanisms, providing a promising next-generation immunotherapeutic in this cancer. Expand
Soluble B-Cell Maturation Antigen Mediates Tumor-Induced Immune Deficiency in Multiple Myeloma
TLDR
The results show that soluble BCMA sequesters circulating BAFF, thereby preventing it from performing its signaling to stimulate normal B-cell and plasma cell development, resulting in reduced polyclonal antibody levels in multiple myeloma patients. Expand
TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease
TLDR
These findings demonstrate the involvement of zTNF4 and its receptors in the development of SLE and identify TACI–Ig as a promising treatment of autoimmune disease in humans. Expand
First-in-human multicenter study of bb2121 anti-BCMA CAR T-cell therapy for relapsed/refractory multiple myeloma: Updated results.
TLDR
CRB-401 (NCT02658929) is a multi-center phase 1 dose escalation trial of bb2121 in patients with relapsed and/or refractory MM who have received ≥ 3 prior regimens, including a proteasome inhibitor and an immunomodulatory agent, or are double-refractory, and have ≥ 50% BCMA expression on plasma cells. Expand
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