Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Vai trò của kháng nguyên trưởng thành B trong sinh học và quản lý, cũng như như một mục tiêu điều trị tiềm năng trong đa u tủy
Tóm tắt
Kháng nguyên trưởng thành B (BCMA) được xác định lần đầu tiên như một thụ thể màng tế bào, được biểu hiện độc quyền trên các tế bào B giai đoạn muộn và tế bào plasma (PC). Các nghiên cứu về BCMA như một mục tiêu can thiệp điều trị trong đa u tủy (MM) đã được khởi xướng vào năm 2007, sử dụng cSG1 như một kháng thể trần (Ab) cũng như một phức hợp kháng thể – thuốc (ADC) nhắm vào BCMA, cuối cùng dẫn đến các nghiên cứu lâm sàng hiện đang diễn ra cho các bệnh nhân MM điều trị trước đó. Kể từ đó, nhiều công ty đã phát triển các ADC nhắm vào BCMA. Ngoài ra, hiện tại có ba kháng thể dị tính đang được phát triển, liên kết với cả BCMA và CD3ε trên tế bào T. Tương tác này dẫn đến việc tuyển mộ và kích hoạt tế bào T, gây ra sự ly giải tế bào mục tiêu. Gần đây hơn, tế bào T đã được kỹ thuật di truyền để nhận biết các tế bào biểu hiện BCMA và vào năm 2013, báo cáo đầu tiên về tế bào T nhận diện kháng nguyên chimeric chống BCMA cho thấy những tế bào này tiêu diệt các dòng tế bào MM và các xenograft MM ở người trong chuột. BCMA cũng được hòa tan trong máu (BCMA hòa tan [sBCMA]) và bệnh nhân MM có bệnh tiến triển có mức sBCMA cao hơn đáng kể so với những bệnh nhân đáp ứng điều trị. sBCMA lưu thông trong máu có thể làm hạn chế hiệu quả của các liệu pháp điều trị hướng tới BCMA. Khi sBCMA liên kết với yếu tố kích thích tế bào B (BAFF), BAFF không thể thực hiện chức năng sinh học chính của nó là kích thích sự tăng trưởng và biệt hóa tế bào B thành tế bào plasma tiết kháng thể. Tuy nhiên, việc sử dụng các chất ức chế γ-secretase, ngăn chặn sự tách ra của BCMA từ các tế bào PC, có thể cải thiện hiệu quả của các liệu pháp nhắm vào BCMA này.
Từ khóa
Tài liệu tham khảo
Laabi Y, Gras MP, Carbonnel F, Brouet JC, Berger R, Larsen CJ, et al. A new gene, BCM, on chromosome 16 is fused to interleukin 2 gene by a t(4;16)(q26;p13) translocation in a malignant T cell lymphoma. EMBO J. 1992;11:3897–904.
Laabi Y, Gras MP, Brouet JC, Berger R, Larsen CJ, Tsapis A. The BCMA gene, preferentially expressed during lymphoid maturation, is bidirectionally transcribed. Nucleic Acids Res. 1994;22:1147–54.
Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, et al. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood. 2004;103:689–94.
Thompson JS, Schneider P, Kalled SL, Wang L, Lefevre EA, Cachero TG, 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.
Seckinger A, Delgado JA, Moser S, Moreno L, Neuber B, Grab A, et al. Target expression, generation, preclinical activity, and pharmacokinetics of the BCMA-T cell bispecific antibody EM801 for multiple myeloma treatment. Cancer Cell. 2017;31:396–410.
Sanchez E, Li M, Kitto A, Li J, Wang CS, Kirk DT, 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.
Pelletier M, Thompson JS, Qian F, Bixler SA, Gong D, Cachero T, et al. Comparison of soluble decoy IgG fusion proteins of BAFF-R and BCMA as antagonists for BAFF. J Biol Chem. 2003;278:33127–33.
Rennert P, Schneider P, Cachero TG, Thompson J, Trabach L, Hertig S, et al. A soluble form of B cell maturation antigen, a receptor for the tumor necrosis family member APRIL, inhibits tumor cell growth. J Exp Med. 2000;192:1677–83.
Schneider P, Mackay F, Steiner V, Hofmann K, Bodmer JL, Holler N, et al. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 1999;189:1747–56.
Yan M, Marsters SA, Grewal IS, Wang H, Ashkenazi A, Dixit VM. Identification of a receptor for BLyS demonstrates a crucial role in humoral immunity. Nat Immunol. 2000;1:37–41.
Schneider P, Takatsuka H, Wilson A, Mackay F, Tardivel A, Lens S, et al. 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.
Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P, et al. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 1999;285:260–3.
Mackay F, Browning JL. BAFF: a fundamental survival factor for B cells. Nat Rev Immunol. 2002;2:465–75.
Avery DT, Kalled SL, Ellyard JI, Ambrose C, Bixler SA, Thien M, et al. BAFF selectively enhances the survival of plasmablasts generated from human memory B cells. J Clin Invest. 2003;112:286–97.
Tai Y-T, Acharya C, An G, Moschetta M, Zhong MY, Feng X, et al. APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment. Blood. 2016;127:3225–36.
O’Connor BP, Raman VS, Erickson LD, Cook WJ, Weaver LK, Ahonen C, et al. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med. 2004;199:91–8.
Moreaux J, Legouffe E, Jourdan E, Quittet P, Reme T, Lugagne C, et al. BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood. 2004;103:3148–57.
Sanchez E, Gillespie AE, Tang G, Ferros M, Harutyunyan NM, Vardanyan S, et al. Soluble B-cell maturation antigen mediates tumor-induced immune deficiency in multiple myeloma. Clin Cancer Res. 2016;22:3383–97.
Mariani G, Strober W. Immunoglobulin metabolism. In: Metzger H, editor. Fc receptors and the action of antibodies. Am Soc Microbiol. 1990. p. 94–180.
Anderson CL, Chaudhury C, Kim J, Bronson CL, Wani MA, Mohanty S. Perspective – FcRn transports albumin: relevance to immunology and medicine. Trends Immunol. 2006;27:343–8.
Udd KA, Soof C, Etessami S, Rahbari A, Gross Z, Casas C, et al. Changes in serum B-cell maturation antigen levels are a rapid and reliable indicator of treatment efficacy for patients with multiple myeloma. In: Proceedings of the 16th International Myeloma Workshop. 2017, New Delhi, India: IMW: p. e27, Abstract nr OP-032.
Jagannath S. Value of free light chain testing for the diagnosis and monitoring of monoclonal gammopathies in hematology. Clin Lymphoma Myeloma. 2007;7:518–23.
Rajkumar SV, Dimpooulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538–48.
Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International myeloma working group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17:e328–46.
Dittrich T, Bochtler T, Kimmich C, Beckner N, Jauch A, Goldschmidt H, et al. AL amyloidosis patients with low amyloidogenic free light chain levels at first diagnosis have an excellent prognostic. Blood. 2017;130:632–42.
Ghermezi M, Li M, Vardanyan S, Harutyunyan N-M, Gottlieb J, Berenson A, et al. Serum B-cell maturation antigen: a novel biomarker to predict outcomes for multiple myeloma patients. Haematologica. 2017;102:785–95.
Fahey JL, Scoggins R, Utz JP, Szwed CF. Infection, antibody response and gamma globulin components in multiple myeloma and macroglobulinemia. Am J Med. 1963;35:698–707.
Cone L, Uhr JW. Immunological deficiency disorders associated with chronic lymphocytic leukemia and multiple myeloma. J Clin Invest. 1964;43:2241–8.
Broder S, Humphrey R, Durm M, Blackman M, Meade B, Goldman C, et al. Impaired synthesis of polyclonal (non-paraprotein) immunoglobulins by circulating lymphocytes from patients with multiple myeloma – role of suppressor cells. N Engl J Med. 1975;293:887–92.
Perri RT, Hebbel RP, Oken MM. Influence of treatment and response status on infection risk in multiple myeloma. Am J Med. 1981;71:935–40.
Kastritis E, Zagouri F, Symeonidis A, Roussou M, Sioni A, Pouli A, et al. Preserved levels of uninvolved immunoglobulins are independently associated with favorable outcome in patients with symptomatic multiple myeloma. Leukemia. 2014;28:2075–9.
Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, et al. TACI and BCMA are receptors for a TNF homologue implicated in B cell autoimmune disease. Nature. 2000;404:995–9.
Hong-Bing S, Johnson H. B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1. PNAS. 2000;97:9156–61.
Laurent SA, Hoffman FS, Kuhn P, Cheng Q, Chu Y, Schmidt-Supprian M, et al. γ-secretase directly sheds the survival receptor BCMA from plasma cells. Nat Commun. 2015;102:785–95.
Vardanyan S, Meid K, Udd KA, Wang J, Li M, Sanchez E, et al. Serum levels of B-cell maturation antigen are elevated in Waldenstrom’s macroglobulinemia patients and correlate with disease status and conventional M-protein and IgM levels. Blood. 2015;126:1778.
Udd KA, Rassenti LA, David ME, Wang J, Linesch J, Li M, et al. Plasma B-cell maturation antigen levels are elevated and correlate with disease activity in patients with chronic lymphocytic leukemia. Blood. 2015;126:2931.
Steri M, Orru V, Idda ML, Pitzalis M, Zara I, Sidore C, et al. Overexpression of the cytokine BAFF and autoimmunity risk. N Engl J Med. 2017;376:1615–26.
Chui A, Xu W, He B, Dillon SR, Gross JA, Sievers E, 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.
Elsawa SF, Novak AJ, Grote DM, Ziesmer SC, Witzig TE, Kyle RA, et al. B-lymphocyte stimulator (BLyS) stimulates immunoglobulin production and malignant B-cell growth in Waldenström macroglobulinemia. Blood. 2006;107:2282–8.
Samy E, Wax S, Huard B, Hess H, Schneider P. Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases. Int Rev Immunol. 2017;36:3–19.
Claudio JO, Masih-Khan E, Tang H, Goncalves J, Voralia M, Li ZH, et al. A molecular compendium of genes expressed in multiple myeloma. Blood. 2002;100:2175–86.
Ryan MC, Hering M, Peckham D, McDonagh CF, Brown L, Kim KM, et al. Antibody targeting of B-cell maturation antigen on malignant plasma cells. Mol Cancer Ther. 2007;6:3009–18.
Tai Y-T, Mayes PA, Chirag A, Zhong MY, Cea M, Cagnetta A, et al. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood. 2014;123:3128–38.
Hipp S, Tai Y-T, Blanset D, Deegen P, Wahl J, Thomas O, et al. A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo. Leukemia. 2017;31(8):1743–51.
Ramadoss NS, Schulman AD, Choi S-H, et al. An anti-B cell maturation antigen bispecific antibody for multiple myeloma. J Am Chem Soc. 2015;137:5288–91.
Moreno L, Zabaleta A, Aliganani D, Lasa M, Maiso P, Jelinek T, et al. New insights into the mechanism of action (MoA) of first-in-class IgG-based BCMA T-cell bispecific antibody (TCB) for the treatment of multiple myeloma (MM). Blood. 2016;128:2096.
Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013;19:2048–60.
Chen H, Li M, Sanchez E, Wang C, Udd KA, Soof CM, et al. Gene expression of gamma secretase (GS) complex-related proteins, the enzyme that sheds B-cell maturation antigen (BCMA), among patients with multiple myeloma (MM) and effects of the GS inhibitor LSN424354 on solubilized BCMA in MM and chronic lymphocytic leukemia. Blood. 2016;128:5641.
Berdeja JG, Lin Y, Raje NS, Siegel DS, Munshi N, Liedtke M, et al. First-in-human multicenter study of bb2121 anti-BCMA CAR T-cell therapy for relapsed/refractory multiple myeloma: updated results. J Clin Oncol. 2017;35(15_suppl):3010.
Fan F, Zhao W, Liu J, He A, Chen Y, Cao X, et al. Durable remissions with BCMA-specific chimeric antigen receptor (CAR)-modified T cells in patients with refractory/relapsed multiple myeloma. J Clin Oncol. 2017;35(18_suppl):3001.