Targeting B-cell maturation antigen in multiple myeloma

Immunotherapy. 2015;7(11):1187-99. doi: 10.2217/imt.15.77. Epub 2015 Sep 15.

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.

Keywords: ADC; B-cell maturation antigen; BCMA; BM; CAR-T; CAR-expressing T cells; Fc-engineered therapeutic antibody; MM; antibody drug conjugate; bone marrow; chimeric antigen receptor; microenvironment; multiple myeloma; targeted immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism*
  • B-Cell Maturation Antigen / immunology
  • B-Cell Maturation Antigen / metabolism*
  • Clinical Trials as Topic
  • Humans
  • Immunotherapy*
  • Molecular Targeted Therapy
  • Multiple Myeloma / immunology
  • Multiple Myeloma / therapy*
  • Oligopeptides / chemistry
  • Protein Engineering
  • Receptors, Antigen, T-Cell / genetics
  • Recombinant Fusion Proteins / genetics
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • B-Cell Maturation Antigen
  • Oligopeptides
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • TNFRSF17 protein, human
  • monomethylauristatin F

Associated data

  • ClinicalTrials.gov/NCT02064387
  • ClinicalTrials.gov/NCT02215967