Paving the Way toward Successful Multiple Myeloma Treatment: Chimeric Antigen Receptor T-Cell Therapy

Cells. 2020 Apr 16;9(4):983. doi: 10.3390/cells9040983.

Abstract

Despite the significant progress of modern anticancer therapies, multiple myeloma (MM) is still incurable for the majority of patients. Following almost three decades of development, chimeric antigen receptor (CAR) T-cell therapy now has the opportunity to revolutionize the treatment landscape and meet the unmet clinical need. However, there are still several major hurdles to overcome. Here we discuss the recent advances of CAR T-cell therapy for MM with an emphasis on future directions and possible risks. Currently, CAR T-cell therapy for MM is at the first stage of clinical studies, and most studies have focused on CAR T cells targeting B cell maturation antigen (BCMA), but other antigens such as cluster of differentiation 138 (CD138, syndecan-1) are also being evaluated. Although this therapy is associated with side effects, such as cytokine release syndrome and neurotoxicity, and relapses have been observed, the benefit-risk balance and huge potential drive the ongoing clinical progress. To fulfill the promise of recent clinical trial success and maximize the potential of CAR T, future efforts should focus on the reduction of side effects, novel targeted antigens, combinatorial uses of different types of CAR T, and development of CAR T cells targeting more than one antigen.

Keywords: BCMA; chimeric antigen receptor T (CAR T); immunotherapy; multiple myeloma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, CD1d / immunology
  • B-Cell Maturation Antigen / immunology*
  • B-Cell Maturation Antigen / metabolism
  • Cell- and Tissue-Based Therapy / methods*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Integrin beta Chains / metabolism
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / therapy*
  • Receptors, Chimeric Antigen / immunology*
  • Receptors, Chimeric Antigen / metabolism
  • Risk Assessment
  • Syndecan-1 / immunology
  • Syndecan-1 / metabolism
  • T-Lymphocytes / immunology*

Substances

  • Antigens, CD1d
  • B-Cell Maturation Antigen
  • CD1D protein, human
  • Integrin beta Chains
  • Receptors, Chimeric Antigen
  • SDC1 protein, human
  • Syndecan-1