CD38 as an immunotherapeutic target in multiple myeloma

Expert Opin Biol Ther. 2018 Dec;18(12):1209-1221. doi: 10.1080/14712598.2018.1544240. Epub 2018 Nov 13.

Abstract

Introduction: Multiple myeloma (MM) is a currently incurable hematologic tumor with heterogeneous clinical behavior and prognosis. During the last years, survival improved due to a better understanding of MM biology and the development of novel drugs, although it still remains unsatisfactory in many cases: new drugs and treatment strategies are needed. CD38 is uniformly expressed at high levels on MM cells and, to a lesser extent, on the surface of normal hematopoietic and non-hematopoietic cells, making this molecule an interesting target for immunotherapeutic approaches.

Areas covered: This review discusses the preclinical and clinical experience on different immunotherapeutic agents targeting CD38 in MM.

Expert opinion: Monoclonal antibodies (mAbs) targeting CD38 are currently changing the treatment scenario in MM, allowing physicians to reach unprecedented results, especially when anti-CD38 mAbs are used in combination with consolidated MM treatments. Other immunotherapies targeting CD38 - such as conjugated anti-CD38 mAbs, bispecific antibodies stimulating T cells to eliminate CD38+ MM cells, and CD38-specific chimeric antigen receptor T cells - are interesting strategies, currently at earlier developmental stages.

Keywords: CAR T cells; CD38; bispecific antibodies; drug conjugates; monoclonal antibodies; multiple myeloma.

Publication types

  • Review

MeSH terms

  • ADP-ribosyl Cyclase 1 / antagonists & inhibitors
  • ADP-ribosyl Cyclase 1 / immunology*
  • ADP-ribosyl Cyclase 1 / physiology*
  • Animals
  • Antibodies, Bispecific / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy
  • Humans
  • Immunotherapy / methods*
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / physiology*
  • Molecular Targeted Therapy / methods*
  • Molecular Targeted Therapy / trends
  • Multiple Myeloma / immunology
  • Multiple Myeloma / therapy*
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Bispecific
  • Antibodies, Monoclonal
  • Membrane Glycoproteins
  • daratumumab
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1