The promise of chimeric antigen receptor (CAR) T cell therapy in multiple myeloma

Cell Immunol. 2019 Nov:345:103964. doi: 10.1016/j.cellimm.2019.103964. Epub 2019 Aug 13.

Abstract

A cure for multiple myeloma (MM), a malignancy of plasma cells, remains elusive. Nearly all myeloma patients will eventually relapse and develop resistance to currently available treatments. There is an unmet medical need to develop novel and effective therapies that can induce sustained responses. Early phase clinical trials using chimeric antigen receptor (CAR) T cell therapy have shown great promise in the treatment of relapsed and/or refractory MM. In this review article, we provide an overview of the CAR constructs, the gene transfer vector systems, and approaches for T cell activation and expansion. We then summarize the outcomes of several early phase clinical trials of CAR T cell therapy in MM and the novel CAR T targets that are under development. Finally, we explore the potential mechanisms that result in disease relapse after CAR T therapy and propose future directions in CAR T therapy in MM.

Keywords: Chimeric antigen receptor; Efficacy; Multiple myeloma; Toxicities; Treatment.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Immunotherapy, Adoptive / trends
  • Multiple Myeloma / immunology
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / therapy*
  • Neoplasm Recurrence, Local
  • Outcome Assessment, Health Care
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Chimeric Antigen / immunology*
  • Receptors, Chimeric Antigen / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen