Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Multiple Myeloma | Review

B-cell maturation antigen targeting strategies in multiple myeloma treatment, advantages and disadvantages

Authors: Shirin Teymouri Nobari, Jafar Nouri Nojadeh, Mehdi Talebi

Published in: Journal of Translational Medicine | Issue 1/2022

Login to get access

Abstract

B cell maturation antigen (BCMA), a transmembrane glycoprotein member of the tumor necrosis factor receptor superfamily 17 (TNFRSF17), highly expressed on the plasma cells of Multiple myeloma (MM) patients, as well as the normal population. BCMA is used as a biomarker for MM. Two members of the TNF superfamily proteins, including B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL), are closely related to BCMA and play an important role in plasma cell survival and progression of MM. Despite the maximum specificity of the monoclonal antibody technologies, introducing the tumor-specific antigen(s) is not applicable for all malignancies, such as MM that there plenty of relatively specific antigens such as GPCR5D, MUC1, SLAMF7 and etc., but higher expression of BCMA on these cells in comparison with normal ones can be regarded as a relatively exclusive marker. Currently, different monoclonal antibody (mAb) technologies applied in anti-MM therapies such as daratuzumab, SAR650984, GSK2857916, and CAR-T cell therapies are some of these tools that are reviewed in the present manuscript. By the way, the structure, function, and signaling of the BCMA and related molecule(s) role in normal plasma cells and MM development, evaluated as well as the potential side effects of its targeting by different CAR-T cells generations. In conclusion, BCMA can be regarded as an ideal molecule to be targeted in immunotherapeutic methods, regarding lower potential systemic and local side effects.
Literature
1.
Mayani H. Hematopoietic and microenvironment alterations in bone marrow from patients with multiple myeloma. Leuk Res. 2013;37:228–9.PubMedCrossRef
2.
Cho SF, Anderson KC, Tai YT. Targeting B cell maturation antigen (BCMA) in multiple myeloma: potential uses of BCMA-based immunotherapy. Front Immunol. 1821;2018:9.
3.
Nikesitch N, Ling SC. Molecular mechanisms in multiple myeloma drug resistance. J Clin Pathol. 2016;69:97–101.PubMedCrossRef
4.
5.
Tai YT, Acharya C, An G, Moschetta M, Zhong MY, Feng X, Cea M, Cagnetta A, Wen K, van Eenennaam H, et al. APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment. Blood. 2016;127:3225–36.PubMedPubMedCentralCrossRef
6.
Neri P, Kumar S, Fulciniti MT, Vallet S, Chhetri S, Mukherjee S, Tai Y, Chauhan D, Tassone P, Venuta S, et al. Neutralizing B-cell activating factor antibody improves survival and inhibits osteoclastogenesis in a severe combined immunodeficient human multiple myeloma model. Clin Cancer Res. 2007;13:5903–9.PubMedCrossRef
7.
Shen X, Guo Y, Qi J, Shi W, Wu X, Ju S. Binding of B-cell maturation antigen to B-cell activating factor induces survival of multiple myeloma cells by activating Akt and JNK signaling pathways. Cell Biochem Funct. 2016;34:104–10.PubMedCrossRef
8.
Moreaux J, Legouffe E, Jourdan E, Quittet P, Rème T, Lugagne C, Moine P, Rossi JF, Klein B, Tarte K. BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood. 2004;103:3148–57.PubMedCrossRef
9.
10.
Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, Richardson PG, Anderson LD Jr, Sutherland HJ, Yong K, et al. Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 2018;19:1641–53.PubMedPubMedCentralCrossRef
11.
Liu J, Zhong JF, Zhang X, Zhang C. Allogeneic CD19-CAR-T cell infusion after allogeneic hematopoietic stem cell transplantation in B cell malignancies. J Hematol Oncol. 2017;10:35–35.PubMedPubMedCentralCrossRef
12.
Sanchez E, Smith EJ, Yashar MA, Patil S, Li M, Porter AL, Tanenbaum EJ, Schlossberg RE, Soof CM, Hekmati T, et al. The Role of B-Cell Maturation Antigen in the Biology and Management of, and as a Potential Therapeutic Target in Multiple Myeloma. Target Oncol. 2018;13:39–47.PubMedCrossRef
13.
Bluhm J, Kieback E, Marino SF, Oden F, Westermann J, Chmielewski M, Abken H, Uckert W, Höpken UE, Rehm A. CAR T cells with enhanced sensitivity to B cell maturation antigen for the targeting of B cell non-Hodgkin’s lymphoma and multiple myeloma. Mol Ther. 2018;26:1906–20.PubMedPubMedCentralCrossRef
14.
Eckhert E, Hewitt R, Liedtke M. B-cell maturation antigen directed monoclonal antibody therapies for multiple myeloma. Immunotherapy. 2019;11:801–11.PubMedCrossRef
15.
Huang HW, Chen CH, Lin CH, Wong CH, Lin KI. B-cell maturation antigen is modified by a single N-glycan chain that modulates ligand binding and surface retention. Proc Natl Acad Sci USA. 2013;110:10928–33.PubMedPubMedCentralCrossRef
16.
Mackay F, Schneider P, Rennert P, Browning J. BAFF AND APRIL: a tutorial on B cell survival. Annu Rev Immunol. 2003;21:231–64.PubMedCrossRef
17.
18.
Madry C, Laabi Y, Callebaut I, Roussel J, Hatzoglou A, Le Coniat M, Mornon JP, Berger R, Tsapis A. The characterization of murine BCMA gene defines it as a new member of the tumor necrosis factor receptor superfamily. Int Immunol. 1998;10:1693–702.PubMedCrossRef
19.
Laâbi Y, Gras MP, Carbonnel F, Brouet JC, Berger R, Larsen CJ, Tsapis A. 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. Embo j. 1992;11:3897–904.PubMedPubMedCentralCrossRef
20.
Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, Walter-Croneck A, Moreau P, Mateos MV, Magen H, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–31.PubMedCrossRef
21.
Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, Gress RE, Hakim FT, Kochenderfer JN. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013;19:2048–60.PubMedPubMedCentralCrossRef
22.
Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell. 2001;104:487–501.PubMedCrossRef
23.
Khare SD, Sarosi I, Xia XZ, McCabe S, Miner K, Solovyev I, Hawkins N, Kelley M, Chang D, Van G, et al. Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice. Proc Natl Acad Sci U S A. 2000;97:3370–5.PubMedPubMedCentralCrossRef
24.
Shu HB, Johnson H. B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1. Proc Natl Acad Sci USA. 2000;97:9156–61.PubMedPubMedCentralCrossRef
25.
O’Connor BP, Raman VS, Erickson LD, Cook WJ, Weaver LK, Ahonen C, Lin LL, Mantchev GT, Bram RJ, Noelle RJ. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med. 2004;199:91–8.PubMedPubMedCentralCrossRef
26.
27.
Varki A. Biological roles of oligosaccharides: all of the theories are correct. Glycobiology. 1993;3:97–130.PubMedCrossRef
28.
Gras MP, Laâbi Y, Linares-Cruz G, Blondel MO, Rigaut JP, Brouet JC, Leca G, Haguenauer-Tsapis R, Tsapis A. BCMAp: an integral membrane protein in the Golgi apparatus of human mature B lymphocytes. Int Immunol. 1995;7:1093–106.PubMedCrossRef
29.
Tai YT, Li XF, Breitkreutz I, Song W, Neri P, Catley L, Podar K, Hideshima T, Chauhan D, Raje N, et al. Role of B-cell-activating factor in adhesion and growth of human multiple myeloma cells in the bone marrow microenvironment. Cancer Res. 2006;66:6675–82.PubMedCrossRef
30.
Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, Ambrose C, Lawton P, Bixler S, Acha-Orbea H, et al. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 1999;189:1747–56.PubMedPubMedCentralCrossRef
31.
Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P, Soppet D, Charters M, Gentz R, Parmelee D, et al. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 1999;285:260–3.PubMedCrossRef
32.
Elsawa SF, Novak AJ, Grote DM, Ziesmer SC, Witzig TE, Kyle RA, Dillon SR, Harder B, Gross JA, Ansell SM. B-lymphocyte stimulator (BLyS) stimulates immunoglobulin production and malignant B-cell growth in Waldenstrom macroglobulinemia. Blood. 2006;107:2882–8.PubMedPubMedCentralCrossRef
33.
Jelinek DF, Darce JR. Human B lymphocyte malignancies: exploitation of BLyS and APRIL and their receptors. Curr Dir Autoimmun. 2005;8:266–88.PubMedCrossRef
34.
Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, Xu W, Parrish-Novak J, Foster D, Lofton-Day C, et al. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature. 2000;404:995–9.PubMedCrossRef
35.
Cheema GS, Roschke V, Hilbert DM, Stohl W. Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum. 2001;44:1313–9.PubMedCrossRef
36.
Zhang J, Roschke V, Baker KP, Wang Z, Alarcón GS, Fessler BJ, Bastian H, Kimberly RP, Zhou T. Cutting edge: a role for B lymphocyte stimulator in systemic lupus erythematosus. J Immunol. 2001;166:6–10.PubMedCrossRef
37.
Kern C, Cornuel JF, Billard C, Tang R, Rouillard D, Stenou V, Defrance T, Ajchenbaum-Cymbalista F, Simonin PY, Feldblum S, Kolb JP. Involvement of BAFF and APRIL in the resistance to apoptosis of B-CLL through an autocrine pathway. Blood. 2004;103:679–88.PubMedCrossRef
38.
He B, Chadburn A, Jou E, Schattner EJ, Knowles DM, Cerutti A. Lymphoma B cells evade apoptosis through the TNF family members BAFF/BLyS and APRIL. J Immunol. 2004;172:3268–79.PubMedCrossRef
39.
Avery DT, Kalled SL, Ellyard JI, Ambrose C, Bixler SA, Thien M, Brink R, Mackay F, Hodgkin PD, Tangye SG. BAFF selectively enhances the survival of plasmablasts generated from human memory B cells. J Clin Investig. 2003;112:286–97.PubMedPubMedCentralCrossRef
40.
Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, Gross JA, Greipp PR, Jelinek DF. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood. 2004;103:689–94.PubMedCrossRef
41.
Feng X, Zhang L, Acharya C, An G, Wen K, Qiu L, Munshi NC, Tai Y-T, Anderson KC. Targeting CD38 Suppresses Induction and Function of T Regulatory Cells to Mitigate Immunosuppression in Multiple Myeloma. Clin Cancer Res. 2017;23:4290–300.PubMedPubMedCentralCrossRef
42.
Dimopoulos MA, Richardson PG, Moreau P, Anderson KC. Current treatment landscape for relapsed and/or refractory multiple myeloma. Nat Rev Clin Oncol. 2015;12:42–54.PubMedCrossRef
43.
Moreaux J, Cremer FW, Reme T, Raab M, Mahtouk K, Kaukel P, Pantesco V, De Vos J, Jourdan E, Jauch A, et al. The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature. Blood. 2005;106:1021–30.PubMedCrossRef
44.
Schneider P, Takatsuka H, Wilson A, Mackay F, Tardivel A, Lens S, Cachero TG, Finke D, Beermann F, Tschopp J. Maturation of marginal zone and follicular B cells requires B cell activating factor of the tumor necrosis factor family and is independent of B cell maturation antigen. J Exp Med. 2001;194:1691–7.PubMedPubMedCentralCrossRef
45.
Patel DR, Wallweber HJ, Yin J, Shriver SK, Marsters SA, Gordon NC, Starovasnik MA, Kelley RF. Engineering an APRIL-specific B cell maturation antigen. J Biol Chem. 2004;279:16727–35.PubMedCrossRef
46.
Moreaux J, Sprynski AC, Dillon SR, Mahtouk K, Jourdan M, Ythier A, Moine P, Robert N, Jourdan E, Rossi JF, Klein B. APRIL and TACI interact with syndecan-1 on the surface of multiple myeloma cells to form an essential survival loop. Eur J Haematol. 2009;83:119–29.PubMedCrossRef
47.
Reijmers RM, Spaargaren M, Pals ST. Heparan sulfate proteoglycans in the control of B cell development and the pathogenesis of multiple myeloma. Febs j. 2013;280:2180–93.PubMedCrossRef
48.
Matthes T, McKee T, Dunand-Sauthier I, Manfroi B, Park S, Passweg J, Huard B. Myelopoiesis dysregulation associated to sustained APRIL production in multiple myeloma-infiltrated bone marrow. Leukemia. 2015;29:1901–8.PubMedCrossRef
49.
Hendriks J, Planelles L, de Jong-Odding J, Hardenberg G, Pals ST, Hahne M, Spaargaren M, Medema JP. Heparan sulfate proteoglycan binding promotes APRIL-induced tumor cell proliferation. Cell Death Differ. 2005;12:637–48.PubMedCrossRef
50.
Ingold K, Zumsteg A, Tardivel A, Huard B, Steiner QG, Cachero TG, Qiang F, Gorelik L, Kalled SL, Acha-Orbea H, et al. Identification of proteoglycans as the APRIL-specific binding partners. J Exp Med. 2005;201:1375–83.PubMedPubMedCentralCrossRef
51.
Novak AJ, Bram RJ, Kay NE, Jelinek DF. Aberrant expression of B-lymphocyte stimulator by B chronic lymphocytic leukemia cells: a mechanism for survival. Blood. 2002;100:2973–9.PubMedCrossRef
52.
Leone P, Berardi S, Frassanito MA, Ria R, De Re V, Cicco S, Battaglia S, Ditonno P, Dammacco F, Vacca A, Racanelli V. Dendritic cells accumulate in the bone marrow of myeloma patients where they protect tumor plasma cells from CD8+ T-cell killing. Blood. 2015;126:1443–51.PubMedPubMedCentralCrossRef
53.
Darce JR, Arendt BK, Wu X, Jelinek DF. Regulated expression of BAFF-binding receptors during human B cell differentiation. J Immunol. 2007;179:7276–86.PubMedCrossRef
54.
Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005;37:829–34.PubMedCrossRef
55.
56.
Benson MJ, Dillon SR, Castigli E, Geha RS, Xu S, Lam KP, Noelle RJ. Cutting edge: the dependence of plasma cells and independence of memory B cells on BAFF and APRIL. J Immunol. 2008;180:3655–9.PubMedCrossRef
57.
Yang M, Hase H, Legarda-Addison D, Varughese L, Seed B, Ting AT. B cell maturation antigen, the receptor for a proliferation-inducing ligand and B cell-activating factor of the TNF family, induces antigen presentation in B cells. J Immunol. 2005;175:2814–24.PubMedCrossRef
58.
Lee L, Draper B, Chaplin N, Philip B, Chin M, Galas-Filipowicz D, Onuoha S, Thomas S, Baldan V, Bughda R, et al. An APRIL-based chimeric antigen receptor for dual targeting of BCMA and TACI in multiple myeloma. Blood. 2018;131:746–58.PubMedPubMedCentralCrossRef
59.
Deng S, Yuan T, Cheng X, Jian R, Jiang J. B-lymphocyte-induced maturation protein1 up-regulates the expression of B-cell maturation antigen in mouse plasma cells. Mol Biol Rep. 2010;37:3747–55.PubMedCrossRef
60.
Xu S, Lam KP. B-cell maturation protein, which binds the tumor necrosis factor family members BAFF and APRIL, is dispensable for humoral immune responses. Mol Cell Biol. 2001;21:4067–74.PubMedPubMedCentralCrossRef
61.
Thompson JS, Schneider P, Kalled SL, Wang L, Lefevre EA, Cachero TG, MacKay F, Bixler SA, Zafari M, Liu ZY, et al. BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation antigen and is important for maintaining the peripheral B cell population. J Exp Med. 2000;192:129–35.PubMedPubMedCentralCrossRef
62.
Laabi Y, Gras MP, Brouet JC, Berger R, Larsen CJ, Tsapis A. The BCMA gene, preferentially expressed during B lymphoid maturation, is bidirectionally transcribed. Nucleic Acids Res. 1994;22:1147–54.PubMedPubMedCentralCrossRef
63.
Dogan A, Siegel D, Tran N, Fu A, Fowler J, Belani R, Landgren O. B-cell maturation antigen expression across hematologic cancers: a systematic literature review. Blood Cancer J. 2020;10:73.PubMedPubMedCentralCrossRef
64.
Friedman KM, Garrett TE, Evans JW, Horton HM, Latimer HJ, Seidel SL, Horvath CJ, Morgan RA. Effective Targeting of Multiple B-Cell Maturation Antigen-Expressing Hematological Malignances by Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor T Cells. Hum Gene Ther. 2018;29:585–601.PubMedPubMedCentralCrossRef
65.
Bu DX, Singh R, Choi EE, Ruella M, Nunez-Cruz S, Mansfield KG, Bennett P, Barton N, Wu Q, Zhang J, et al. Pre-clinical validation of B cell maturation antigen (BCMA) as a target for T cell immunotherapy of multiple myeloma. Oncotarget. 2018;9:25764–80.PubMedPubMedCentralCrossRef
66.
Lee L, Bounds D, Paterson J, Herledan G, Sully K, Seestaller-Wehr LM, Fieles WE, Tunstead J, McCahon L, Germaschewski FM, et al. Evaluation of B cell maturation antigen as a target for antibody drug conjugate mediated cytotoxicity in multiple myeloma. Br J Haematol. 2016;174:911–22.PubMedCrossRef
67.
Reghunathan R, Bi C, Liu SC, Loong KT, Chung TH, Huang G, Chng WJ. Clonogenic multiple myeloma cells have shared stemness signature associated with patient survival. Oncotarget. 2013;4:1230–40.PubMedPubMedCentralCrossRef
68.
Chiu A, Xu W, He B, Dillon SR, Gross JA, Sievers E, Qiao X, Santini P, Hyjek E, Lee JW, et al. Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL. Blood. 2007;109:729–39.PubMedPubMedCentralCrossRef
69.
Morgan GJ, Walker BA, Davies FE. The genetic architecture of multiple myeloma. Nat Rev Cancer. 2012;12:335–48.PubMedCrossRef
70.
Fowler JA, Mundy GR, Lwin ST, Edwards CM. Bone marrow stromal cells create a permissive microenvironment for myeloma development: a new stromal role for Wnt inhibitor Dkk1. Cancer Res. 2012;72:2183–9.PubMedPubMedCentralCrossRef
71.
Hideshima T, Mitsiades C, Tonon G, Richardson PG, Anderson KC. Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer. 2007;7:585–98.PubMedCrossRef
72.
Rennert P, Schneider P, Cachero TG, Thompson J, Trabach L, Hertig S, Holler N, Qian F, Mullen C, Strauch K, et al. A soluble form of B cell maturation antigen, a receptor for the tumor necrosis factor family member APRIL, inhibits tumor cell growth. J Exp Med. 2000;192:1677–84.PubMedPubMedCentralCrossRef
73.
Alexaki VI, Notas G, Pelekanou V, Kampa M, Valkanou M, Theodoropoulos P, Stathopoulos EN, Tsapis A, Castanas E. Adipocytes as immune cells: differential expression of TWEAK, BAFF, and APRIL and their receptors (Fn14, BAFF-R, TACI, and BCMA) at different stages of normal and pathological adipose tissue development. J Immunol. 2009;183:5948–56.PubMedCrossRef
74.
Pelekanou V, Notas G, Kampa M, Tsentelierou E, Stathopoulos EN, Tsapis A, Castanas E. BAFF, APRIL, TWEAK, BCMA, TACI and Fn14 proteins are related to human glioma tumor grade: immunohistochemistry and public microarray data meta-analysis. PLoS ONE. 2013;8:e83250.PubMedPubMedCentralCrossRef
75.
Avery DT, Kalled SL, Ellyard JI, Ambrose C, Bixler SA, Thien M, Brink R, Mackay F, Hodgkin PD, Tangye SG. BAFF selectively enhances the survival of plasmablasts generated from human memory B cells. J Clin Invest. 2003;112:286–97.PubMedPubMedCentralCrossRef
76.
Milone MC, Fish JD, Carpenito C, Carroll RG, Binder GK, Teachey D, Samanta M, Lakhal M, Gloss B, Danet-Desnoyers G, et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther. 2009;17:1453–64.PubMedPubMedCentralCrossRef
77.
Chauhan D, Singh AV, Brahmandam M, Carrasco R, Bandi M, Hideshima T, Bianchi G, Podar K, Tai Y-T, Mitsiades C, et al. Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target. Cancer Cell. 2009;16:309–23.PubMedPubMedCentralCrossRef
78.
Tai YT, Mayes PA, Acharya C, Zhong MY, Cea M, Cagnetta A, Craigen J, Yates J, Gliddon L, Fieles W, et al. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood. 2014;123:3128–38.PubMedPubMedCentralCrossRef
79.
Pont MJ, Hill T, Cole GO, Abbott JJ, Kelliher J, Salter AI, Hudecek M, Comstock ML, Rajan A, Patel BKR, et al. γ-Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma. Blood. 2019;134:1585–97.PubMedPubMedCentralCrossRef
80.
Laurent SA, Hoffmann FS, Kuhn PH, Cheng Q, Chu Y, Schmidt-Supprian M, Hauck SM, Schuh E, Krumbholz M, Rübsamen H, et al. γ-Secretase directly sheds the survival receptor BCMA from plasma cells. Nat Commun. 2015;6:7333.PubMedCrossRef
81.
Bellucci R, Alyea EP, Chiaretti S, Wu CJ, Zorn E, Weller E, Wu B, Canning C, Schlossman R, Munshi NC, et al. Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor. Blood. 2005;105:3945–50.PubMedPubMedCentralCrossRef
82.
Vardanyan S, Meid K, Udd K, Wang J, Li M, Sanchez E, Wang C, Gillespie A, Spitzer M, Spektor T, et al. Serum Levels of B-Cell Maturation Antigen Are Elevated in Waldenström’s Macroglobulinemia Patients and Correlate with Disease Status and Conventional M-Protein and IgM Levels. Blood. 2015;126:1778–1778.CrossRef
83.
Sanchez E, Li M, Kitto A, Li J, Wang CS, Kirk DT, Yellin O, Nichols CM, Dreyer MP, Ahles CP, et al. Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival. Br J Haematol. 2012;158:727–38.PubMedCrossRef
84.
Sanchez E, Gillespie A, Tang G, Ferros M, Harutyunyan NM, Vardanyan S, Gottlieb J, Li M, Wang CS, Chen H, Berenson JR. Soluble B-Cell Maturation Antigen Mediates Tumor-Induced Immune Deficiency in Multiple Myeloma. Clin Cancer Res. 2016;22:3383–97.PubMedCrossRef
85.
Darce JR, Arendt BK, Chang SK, Jelinek DF. Divergent effects of BAFF on human memory B cell differentiation into Ig-secreting cells. J Immunol. 2007;178:5612–22.PubMedCrossRef
86.
von Bülow G-U, Bram RJ. NF-AT Activation Induced by a CAML-Interacting Member of the Tumor Necrosis Factor Receptor Superfamily. Science. 1997;278:138–41.CrossRef
87.
Thompson JS, Bixler SA, Qian F, Vora K, Scott ML, Cachero TG, Hession C, Schneider P, Sizing ID, Mullen C, et al. BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF. Science. 2001;293:2108–11.PubMedCrossRef
88.
Yan M, Brady JR, Chan B, Lee WP, Hsu B, Harless S, Cancro M, Grewal IS, Dixit VM. Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency. Curr Biol. 2001;11:1547–52.PubMedCrossRef
89.
Bischof D, Elsawa SF, Mantchev G, Yoon J, Michels GE, Nilson A, Sutor SL, Platt JL, Ansell SM, von Bulow G, Bram RJ. Selective activation of TACI by syndecan-2. Blood. 2006;107:3235–42.PubMedPubMedCentralCrossRef
90.
Gorelik L, Cutler AH, Thill G, Miklasz SD, Shea DE, Ambrose C, Bixler SA, Su L, Scott ML, Kalled SL. Cutting edge: BAFF regulates CD21/35 and CD23 expression independent of its B cell survival function. J Immunol. 2004;172:762–6.PubMedCrossRef
91.
Reichlin A, Hu Y, Meffre E, Nagaoka H, Gong S, Kraus M, Rajewsky K, Nussenzweig MC. B cell development is arrested at the immature B cell stage in mice carrying a mutation in the cytoplasmic domain of immunoglobulin beta. J Exp Med. 2001;193:13–23.PubMedPubMedCentralCrossRef
92.
Schiemann B, Gommerman JL, Vora K, Cachero TG, Shulga-Morskaya S, Dobles M, Frew E, Scott ML. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science. 2001;293:2111–4.PubMedCrossRef
93.
Shulga-Morskaya S, Dobles M, Walsh ME, Ng LG, MacKay F, Rao SP, Kalled SL, Scott ML. B cell-activating factor belonging to the TNF family acts through separate receptors to support B cell survival and T cell-independent antibody formation. J Immunol. 2004;173:2331–41.PubMedCrossRef
94.
Seshasayee D, Valdez P, Yan M, Dixit VM, Tumas D, Grewal IS. Loss of TACI Causes Fatal Lymphoproliferation and Autoimmunity, Establishing TACI as an Inhibitory BLyS Receptor. Immunity. 2003;18:279–88.PubMedCrossRef
95.
Hatzoglou A, Roussel J, Bourgeade MF, Rogier E, Madry C, Inoue J, Devergne O, Tsapis A. TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. J Immunol. 2000;165:1322–30.PubMedCrossRef
96.
Bossen C, Schneider P. BAFF, APRIL and their receptors: structure, function and signaling. Semin Immunol. 2006;18:263–75.PubMedCrossRef
97.
Rickert R, Jellusova J: TNF and TNFR Family Members and B Cell Activation. Encyclopedia of Immunobiology 2016.
98.
Patke A, Mecklenbräuker I, Erdjument-Bromage H, Tempst P, Tarakhovsky A. BAFF controls B cell metabolic fitness through a PKC beta- and Akt-dependent mechanism. J Exp Med. 2006;203:2551–62.PubMedPubMedCentralCrossRef
99.
100.
Senftleben U, Cao Y, Xiao G, Greten FR, Krähn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun SC, Karin M. Activation by IKKalpha of a second, evolutionary conserved NF-kappa B signaling pathway. Science. 2001;293:1495–9.PubMedCrossRef
101.
102.
Liao G, Zhang M, Harhaj EW, Sun SC. Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J Biol Chem. 2004;279:26243–50.PubMedCrossRef
103.
Vallabhapurapu S, Matsuzawa A, Zhang W, Tseng PH, Keats JJ, Wang H, Vignali DA, Bergsagel PL, Karin M. Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling. Nat Immunol. 2008;9:1364–70.PubMedPubMedCentralCrossRef
104.
Yamada T, Mitani T, Yorita K, Uchida D, Matsushima A, Iwamasa K, Fujita S, Matsumoto M. Abnormal immune function of hemopoietic cells from alymphoplasia (aly) mice, a natural strain with mutant NF-kappa B-inducing kinase. J Immunol. 2000;165:804–12.PubMedCrossRef
105.
Hatada EN, Do RK, Orlofsky A, Liou HC, Prystowsky M, MacLennan IC, Caamano J, Chen-Kiang S. NF-kappa B1 p50 is required for BLyS attenuation of apoptosis but dispensable for processing of NF-kappa B2 p100 to p52 in quiescent mature B cells. J Immunol. 2003;171:761–8.PubMedCrossRef
106.
Sommer K, Guo B, Pomerantz JL, Bandaranayake AD, Moreno-García ME, Ovechkina YL, Rawlings DJ. Phosphorylation of the CARMA1 linker controls NF-kappaB activation. Immunity. 2005;23:561–74.PubMedCrossRef
107.
Zarnegar B, Yamazaki S, He JQ, Cheng G. Control of canonical NF-kappaB activation through the NIK-IKK complex pathway. Proc Natl Acad Sci USA. 2008;105:3503–8.PubMedPubMedCentralCrossRef
108.
O’Mahony A, Lin X, Geleziunas R, Greene WC. Activation of the heterodimeric IkappaB kinase alpha (IKKalpha)-IKKbeta complex is directional: IKKalpha regulates IKKbeta under both basal and stimulated conditions. Mol Cell Biol. 2000;20:1170–8.PubMedPubMedCentralCrossRef
109.
Rickert RC, Jellusova J, Miletic AV. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev. 2011;244:115–33.PubMedPubMedCentralCrossRef
110.
Jellusova J, Miletic AV, Cato MH, Lin W-W, Hu Y, Bishop GA, Shlomchik MJ, Rickert RC. Context-specific BAFF-R signaling by the NF-κB and PI3K pathways. Cell Rep. 2013;5:1022–35.PubMedCrossRef
111.
Woodland RT, Fox CJ, Schmidt MR, Hammerman PS, Opferman JT, Korsmeyer SJ, Hilbert DM, Thompson CB. Multiple signaling pathways promote B lymphocyte stimulator dependent B-cell growth and survival. Blood. 2008;111:750–60.PubMedPubMedCentralCrossRef
112.
Fruman DA, Cantley LC. Phosphoinositide 3-kinase in immunological systems. Semin Immunol. 2002;14:7–18.PubMedCrossRef
113.
Leslie NR, Downes CP. PTEN: The down side of PI 3-kinase signalling. Cell Signal. 2002;14:285–95.PubMedCrossRef
114.
Henley T, Kovesdi D, Turner M. B-cell responses to B-cell activation factor of the TNF family (BAFF) are impaired in the absence of PI3K delta. Eur J Immunol. 2008;38:3543–8.PubMedCrossRef
115.
Khan WN. B cell receptor and BAFF receptor signaling regulation of B cell homeostasis. J Immunol. 2009;183:3561–7.PubMedCrossRef
116.
Shinners NP, Carlesso G, Castro I, Hoek KL, Corn RA, Woodland RT, Scott ML, Wang D, Khan WN. Bruton’s tyrosine kinase mediates NF-kappa B activation and B cell survival by B cell-activating factor receptor of the TNF-R family. J Immunol. 2007;179:3872–80.PubMedCrossRef
117.
Maurer U, Charvet C, Wagman AS, Dejardin E, Green DR. Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol Cell. 2006;21:749–60.PubMedCrossRef
118.
Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 1999;96:857–68.PubMedCrossRef
119.
Dengler HS, Baracho GV, Omori SA, Bruckner S, Arden KC, Castrillon DH, DePinho RA, Rickert RC. Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation. Nat Immunol. 2008;9:1388–98.PubMedPubMedCentralCrossRef
120.
You H, Pellegrini M, Tsuchihara K, Yamamoto K, Hacker G, Erlacher M, Villunger A, Mak TW. FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal. J Exp Med. 2006;203:1657–63.PubMedPubMedCentralCrossRef
121.
Dijkers PF, Medema RH, Lammers JW, Koenderman L, Coffer PJ. Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1. Curr Biol. 2000;10:1201–4.PubMedCrossRef
122.
Elgueta R, Benson MJ, de Vries VC, Wasiuk A, Guo Y, Noelle RJ. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev. 2009;229:152–72.PubMedCrossRef
123.
Schwartz MA, Kolhatkar NS, Thouvenel C, Khim S, Rawlings DJ. CD4+ T cells and CD40 participate in selection and homeostasis of peripheral B cells. J Immunol. 2014;193:3492–502.PubMedPubMedCentralCrossRef
124.
Bishop GA, Hostager BS. The CD40-CD154 interaction in B cell-T cell liaisons. Cytokine Growth Factor Rev. 2003;14:297–309.PubMedCrossRef
125.
Erickson LD, Durell BG, Vogel LA, O’Connor BP, Cascalho M, Yasui T, Kikutani H, Noelle RJ. Short-circuiting long-lived humoral immunity by the heightened engagement of CD40. J Clin Investig. 2002;109:613–20.PubMedPubMedCentralCrossRef
126.
Zarnegar B, He JQ, Oganesyan G, Hoffmann A, Baltimore D, Cheng G. Unique CD40-mediated biological program in B cell activation requires both type 1 and type 2 NF-kappaB activation pathways. Proc Natl Acad Sci U S A. 2004;101:8108–13.PubMedPubMedCentralCrossRef
127.
Ren CL, Morio T, Fu SM, Geha RS. Signal transduction via CD40 involves activation of lyn kinase and phosphatidylinositol-3-kinase, and phosphorylation of phospholipase C gamma 2. J Exp Med. 1994;179:673–80.PubMedCrossRef
128.
Gallagher E, Enzler T, Matsuzawa A, Anzelon-Mills A, Otero D, Holzer R, Janssen E, Gao M, Karin M. Kinase MEKK1 is required for CD40-dependent activation of the kinases Jnk and p38, germinal center formation, B cell proliferation and antibody production. Nat Immunol. 2007;8:57–63.PubMedCrossRef
129.
Leo E, Welsh K, Matsuzawa S, Zapata JM, Kitada S, Mitchell RS, Ely KR, Reed JC. Differential requirements for tumor necrosis factor receptor-associated factor family proteins in CD40-mediated induction of NF-kappaB and Jun N-terminal kinase activation. J Biol Chem. 1999;274:22414–22.PubMedCrossRef
130.
Pullen SS, Miller HG, Everdeen DS, Dang TT, Crute JJ, Kehry MR. CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions: regulation of CD40 signaling through multiple TRAF binding sites and TRAF hetero-oligomerization. Biochemistry. 1998;37:11836–45.PubMedCrossRef
131.
132.
133.
Hahne M, Kataoka T, Schröter M, Hofmann K, Irmler M, Bodmer JL, Schneider P, Bornand T, Holler N, French LE, et al. APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth. J Exp Med. 1998;188:1185–90.PubMedPubMedCentralCrossRef
134.
Alexopoulou AN, Multhaupt HA, Couchman JR. Syndecans in wound healing, inflammation and vascular biology. Int J Biochem Cell Biol. 2007;39:505–28.PubMedCrossRef
135.
Bolkun L, Lemancewicz D, Jablonska E, Kulczynska A, Bolkun-Skornicka U, Kloczko J, Dzieciol J. BAFF and APRIL as TNF superfamily molecules and angiogenesis parallel progression of human multiple myeloma. Ann Hematol. 2014;93:635–44.PubMedCrossRef
136.
Yu G, Boone T, Delaney J, Hawkins N, Kelley M, Ramakrishnan M, McCabe S, Qiu WR, Kornuc M, Xia XZ, et al. APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity. Nat Immunol. 2000;1:252–6.PubMedCrossRef
137.
Annunziata CM, Davis RE, Demchenko Y, Bellamy W, Gabrea A, Zhan F, Lenz G, Hanamura I, Wright G, Xiao W, et al. Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma. Cancer Cell. 2007;12:115–30.PubMedPubMedCentralCrossRef
138.
Keats JJ, Fonseca R, Chesi M, Schop R, Baker A, Chng WJ, Van Wier S, Tiedemann R, Shi CX, Sebag M, et al. Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. Cancer Cell. 2007;12:131–44.PubMedPubMedCentralCrossRef
139.
Häcker H, Tseng PH, Karin M. Expanding TRAF function: TRAF3 as a tri-faced immune regulator. Nat Rev Immunol. 2011;11:457–68.PubMedCrossRef
140.
Richardson PG, Mitsiades C, Hideshima T, Anderson KC. Bortezomib: proteasome inhibition as an effective anticancer therapy. Annu Rev Med. 2006;57:33–47.PubMedCrossRef
141.
Rodriguez-Abreu D, Bordoni A, Zucca E. Epidemiology of hematological malignancies. Ann Oncol. 2007;18(Suppl 1):i3–8.PubMedCrossRef
142.
Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, Fonseca R, Rajkumar SV, Offord JR, Larson DR, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78:21–33.PubMedCrossRef
143.
144.
Manier S, Salem KZ, Park J, Landau DA, Getz G, Ghobrial IM. Genomic complexity of multiple myeloma and its clinical implications. Nat Rev Clin Oncol. 2017;14:100–13.PubMedCrossRef
145.
146.
Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, de la Rubia J, Granell M, Besalduch J, Palomera L, González Y, et al. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012;120:1589–96.PubMedCrossRef
147.
Laubach JP, Voorhees PM, Hassoun H, Jakubowiak A, Lonial S, Richardson PG. Current strategies for treatment of relapsed/refractory multiple myeloma. Expert Rev Hematol. 2014;7:97–111.PubMedCrossRef
148.
Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352:2487–98.PubMedCrossRef
149.
Richardson PG, Jagannath S, Moreau P, Jakubowiak AJ, Raab MS, Facon T, Vij R, White D, Reece DE, Benboubker L, et al. Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b–2 dose-escalation study. Lancet Haematol. 2015;2:e516-527.PubMedPubMedCentralCrossRef
150.
Deckert J, Wetzel MC, Bartle LM, Skaletskaya A, Goldmacher VS, Vallée F, Zhou-Liu Q, Ferrari P, Pouzieux S, Lahoute C, et al. SAR650984, a novel humanized CD38-targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other CD38+ hematologic malignancies. Clin Cancer Res. 2014;20:4574–83.PubMedCrossRef
151.
Kinneer K, Meekin J, Tiberghien AC: SLC46A3 as a Potential Predictive Biomarker for Antibody-Drug Conjugates Bearing Noncleavable Linked Maytansinoid and Pyrrolobenzodiazepine Warheads. 2018, 24:6570–6582.
152.
Alley SC, Okeley NM, Senter PD. Antibody-drug conjugates: targeted drug delivery for cancer. Curr Opin Chem Biol. 2010;14:529–37.PubMedCrossRef
153.
de Oca RMAA, Vitali N, Bhattacharya S, Blackwell C, Patel K, Seestaller-Wehr L, Kaczynski H, Shi H, Dobrzynski E, Obert L. Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-mediated Antitumor Responses In Vivo. Mol Cancer Ther. 2021;20(10):1941–55.CrossRef
154.
Trudel SLN, Popat R, Voorhees PM, Reeves B, Libby EN, Richardson PG, Anderson LD Jr, Sutherland HJ, Yong K, Hoos A. Targeting B-cell maturation antigen with GSK2857916 antibody–drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 2018;19(12):1641–53.PubMedPubMedCentralCrossRef
155.
156.
Dudley ME, Wunderlich JR, Shelton TE, Even J, Rosenberg SA. Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J Immunother. 2003;26:332–42.PubMedPubMedCentralCrossRef
157.
158.
Sadelain M, Rivière I, Brentjens R. Targeting tumours with genetically enhanced T lymphocytes. Nat Rev Cancer. 2003;3:35–45.PubMedCrossRef
159.
Irving BA, Weiss A. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways. Cell. 1991;64:891–901.PubMedCrossRef
160.
161.
Rossjohn J, Gras S, Miles JJ, Turner SJ, Godfrey DI, McCluskey J. T cell antigen receptor recognition of antigen-presenting molecules. Annu Rev Immunol. 2015;33:169–200.PubMedCrossRef
162.
163.
Maher J, Brentjens RJ, Gunset G, Rivière I, Sadelain M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor. Nat Biotechnol. 2002;20:70–5.PubMedCrossRef
164.
Hombach A, Wieczarkowiecz A, Marquardt T, Heuser C, Usai L, Pohl C, Seliger B, Abken H. Tumor-specific T cell activation by recombinant immunoreceptors: CD3 zeta signaling and CD28 costimulation are simultaneously required for efficient IL-2 secretion and can be integrated into one combined CD28/CD3 zeta signaling receptor molecule. J Immunol. 2001;167:6123–31.PubMedCrossRef
165.
Imai C, Mihara K, Andreansky M, Nicholson IC, Pui CH, Geiger TL, Campana D. Chimeric receptors with 4–1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia. 2004;18:676–84.PubMedCrossRef
166.
Song DG, Ye Q, Poussin M, Harms GM, Figini M, Powell DJ Jr. CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo. Blood. 2012;119:696–706.PubMedCrossRef
167.
Hombach AA, Abken H. Of chimeric antigen receptors and antibodies: OX40 and 41BB costimulation sharpen up T cell-based immunotherapy of cancer. Immunotherapy. 2013;5:677–81.PubMedCrossRef
168.
Hombach AA, Heiders J, Foppe M, Chmielewski M, Abken H. OX40 costimulation by a chimeric antigen receptor abrogates CD28 and IL-2 induced IL-10 secretion by redirected CD4(+) T cells. Oncoimmunology. 2012;1:458–66.PubMedPubMedCentralCrossRef
169.
Chmielewski M, Abken H. TRUCKs: the fourth generation of CARs. Expert Opin Biol Ther. 2015;15:1145–54.PubMedCrossRef
170.
Hurton LV, Singh H, Najjar AM, Switzer KC, Mi T, Maiti S, Olivares S, Rabinovich B, Huls H, Forget MA, et al. Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells. Proc Natl Acad Sci U S A. 2016;113:E7788-e7797.PubMedPubMedCentralCrossRef
171.
172.
173.
174.
Moreau P, Sonneveld P, Boccadoro M, Cook G, Mateos MV, Nahi H, Goldschmidt H, Dimopoulos MA, Lucio P, Bladé J, et al. Chimeric antigen receptor T-cell therapy for multiple myeloma: a consensus statement from The European Myeloma Network. Haematologica. 2019;104:2358–60.PubMedPubMedCentralCrossRef
175.
176.
177.
Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368:1509–18.PubMedPubMedCentralCrossRef
178.
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017;377:2531–44.PubMedPubMedCentralCrossRef
179.
Posey AD Jr, Schwab RD, Boesteanu AC, Steentoft C, Mandel U, Engels B, Stone JD, Madsen TD, Schreiber K, Haines KM, et al. Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma. Immunity. 2016;44:1444–54.PubMedPubMedCentralCrossRef
180.
Hosen N, Matsunaga Y, Hasegawa K, Matsuno H, Nakamura Y, Makita M, Watanabe K, Yoshida M, Satoh K, Morimoto S, et al. The activated conformation of integrin β(7) is a novel multiple myeloma-specific target for CAR T cell therapy. Nat Med. 2017;23:1436–43.PubMedCrossRef
181.
Brudno JN, Maric I, Hartman SD, Rose JJ, Wang M, Lam N, Stetler-Stevenson M, Salem D, Yuan C, Pavletic S, et al. T cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J Clin Oncol. 2018;36:2267–80.PubMedPubMedCentralCrossRef
182.
Xu J, Chen LJ, Yang SS, Sun Y, Wu W, Liu YF, Xu J, Zhuang Y, Zhang W, Weng XQ, et al. Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma. Proc Natl Acad Sci USA. 2019;116:9543–51.PubMedPubMedCentralCrossRef
Metadata
Title
B-cell maturation antigen targeting strategies in multiple myeloma treatment, advantages and disadvantages
Authors
Shirin Teymouri Nobari
Jafar Nouri Nojadeh
Mehdi Talebi
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03285-y

Other articles of this Issue 1/2022

Journal of Translational Medicine 1/2022 Go to the issue

Research

Simultaneous measurement of the size and methylation of chromosome 4qA-D4Z4 repeats in facioscapulohumeral muscular dystrophy by long-read sequencing

Research

Asprosin inhibits macrophage lipid accumulation and reduces atherosclerotic burden by up-regulating ABCA1 and ABCG1 expression via the p38/Elk-1 pathway

Research

A new nutraceutical (Livogen Plus®) improves liver steatosis in adults with non-alcoholic fatty liver disease

Research

Total mutational load and clinical features as predictors of the metastatic status in lung adenocarcinoma and squamous cell carcinoma patients

Review

β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells?

Research

LncRNA NEAT1 facilitates glioma progression via stabilizing PGK1
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits