Targeting B-cell Maturation Antigen in Multiple Myeloma

Overview

Journal Immunotherapy

Specialties Allergy & Immunology
Pharmacology

Date 2015 Sep 16

PMID 26370838

Citations 111

Authors

Yu-Tzu Tai

Kenneth C Anderson

Affiliations

Soon will be listed here.

Abstract

Novel effective immunotherapies are needed for patients with multiple myeloma (MM), since disease recurrence remains a major obstacle. B-cell maturation antigen (BCMA), a cell surface protein universally expressed on malignant plasma cells , has emerged as a very selective antigen to be targeted in novel treatments for MM. We here first review BCMA-related biology, and then highlight the recent clinical development of a novel afucosylated anti-BCMA monoclonal antibody conjugated with monomethyl auristatin F via noncleavable linker (GSK2857916). Chimeric antigen receptor-expressing T cells targeting BCMA may also induce specific and durable anti-MM responses by patients' own effector cells. Clinical trials testing these two approaches (NCT02064387, NCT02215967) are currently ongoing in relapsed and refractory MM patients.

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References

Tai Y, Mayes P, Acharya C, Zhong M, Cea M, Cagnetta A . Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood. 2014; 123(20):3128-38. PMC: 4023420. DOI: 10.1182/blood-2013-10-535088. View

Oak E, Bartlett N . Blinatumomab for the treatment of B-cell lymphoma. Expert Opin Investig Drugs. 2015; 24(5):715-24. DOI: 10.1517/13543784.2015.1021415. View

Aref S, Azmy E, El-Gilany A . Upregulation of CD200 is associated with regulatory T cell expansion and disease progression in multiple myeloma. Hematol Oncol. 2015; 35(1):51-57. DOI: 10.1002/hon.2206. View

Moreaux J, Sprynski A, Dillon S, Mahtouk K, Jourdan M, Ythier A . 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(2):119-29. DOI: 10.1111/j.1600-0609.2009.01262.x. View

Chu J, Deng Y, Benson D, He S, Hughes T, Zhang J . CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma. Leukemia. 2013; 28(4):917-27. PMC: 3967004. DOI: 10.1038/leu.2013.279. View

Darce J, Arendt B, Chang S, Jelinek D . Divergent effects of BAFF on human memory B cell differentiation into Ig-secreting cells. J Immunol. 2007; 178(9):5612-22. DOI: 10.4049/jimmunol.178.9.5612. View

Gatto B . Atacicept, a homodimeric fusion protein for the potential treatment of diseases triggered by plasma cells. Curr Opin Investig Drugs. 2008; 9(11):1216-27. View

Alici E . IPH-2101, a fully human anti-NK-cell inhibitory receptor mAb for the potential treatment of hematological cancers. Curr Opin Mol Ther. 2010; 12(6):724-33. View

de Weers M, Tai Y, van der Veer M, Bakker J, Vink T, Jacobs D . Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2010; 186(3):1840-8. DOI: 10.4049/jimmunol.1003032. View

10.

Claudio J, Masih-Khan E, Tang H, Goncalves J, Voralia M, Li Z . A molecular compendium of genes expressed in multiple myeloma. Blood. 2002; 100(6):2175-86. DOI: 10.1182/blood-2002-01-0008. View

11.

Jiang H, Zhang W, Shang P, Zhang H, Fu W, Ye F . Transfection of chimeric anti-CD138 gene enhances natural killer cell activation and killing of multiple myeloma cells. Mol Oncol. 2014; 8(2):297-310. PMC: 5528539. DOI: 10.1016/j.molonc.2013.12.001. View

12.

Tai Y, Horton H, Kong S, Pong E, Chen H, Cemerski S . Potent in vitro and in vivo activity of an Fc-engineered humanized anti-HM1.24 antibody against multiple myeloma via augmented effector function. Blood. 2012; 119(9):2074-82. PMC: 3757461. DOI: 10.1182/blood-2011-06-364521. View

13.

Sanchez E, Li M, Kitto A, Li J, Wang C, Kirk D . Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival. Br J Haematol. 2012; 158(6):727-38. DOI: 10.1111/j.1365-2141.2012.09241.x. View

14.

Benson Jr D, Bakan C, Zhang S, Collins S, Liang J, Srivastava S . IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect. Blood. 2011; 118(24):6387-91. PMC: 3490103. DOI: 10.1182/blood-2011-06-360255. View

15.

Kung Sutherland M, Sanderson R, Gordon K, Andreyka J, Cerveny C, Yu C . Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates. J Biol Chem. 2006; 281(15):10540-7. DOI: 10.1074/jbc.M510026200. View

16.

Dimopoulos M, Terpos E . Hematology: first-line bortezomib benefits patients with multiple myeloma. Nat Rev Clin Oncol. 2009; 6(12):683-5. DOI: 10.1038/nrclinonc.2009.171. View

17.

Richardson P, Mitsiades C . Bortezomib: proteasome inhibition as an effective anticancer therapy. Future Oncol. 2006; 1(2):161-71. DOI: 10.1517/14796694.1.2.161. View

18.

Moreaux J, Hose D, Reme T, Jourdan E, Hundemer M, Legouffe E . CD200 is a new prognostic factor in multiple myeloma. Blood. 2006; 108(13):4194-7. DOI: 10.1182/blood-2006-06-029355. View

19.

Maus M, June C . CARTs on the road for myeloma. Clin Cancer Res. 2014; 20(15):3899-901. PMC: 4119563. DOI: 10.1158/1078-0432.CCR-14-0721. View

20.

Hideshima T, Mitsiades C, Tonon G, Richardson P, Anderson K . Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer. 2007; 7(8):585-98. DOI: 10.1038/nrc2189. View