Targeting GPRC5D for multiple myeloma therapy

J Hematol Oncol. 2024 Sep 28;17(1):88. doi: 10.1186/s13045-024-01611-z.

Abstract

Given its nearly ubiquitous expression on plasma cells and limited expression on essential normal tissue, the G protein-coupled receptor class C group 5 member D (GPRC5D) presents a promising opportunity for utilization as an immunotherapy target in multiple myeloma (MM). The therapeutic strategies targeting GPRC5D, such as bispecific antibodies (BsAbs), chimeric antigen receptor (CAR) T cells, and antibody-drug conjugates (ADCs), have been prominently emphasized in relapsed/refractory MM (R/R MM) in recent years. Further clinical trials are necessary to confirm the long-term efficacy of GPRC5D-targeting immunotherapies alone, explore their potentials co-targeting with other specific antigens, or investigate their combinations with existing treatments to overcome MM resistance. This review provides an overview of current research progress in GPRC5D, encompassing its biological characteristics and translational journey from laboratory to clinical application.

Keywords: Bispecific antibodies; Chimeric antigen receptor T cell; G protein-coupled receptor class C group 5 member D; Immunotherapy; Multiple myeloma.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Bispecific / therapeutic use
  • Humans
  • Immunoconjugates / therapeutic use
  • Immunotherapy / methods
  • Molecular Targeted Therapy / methods
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / immunology
  • Multiple Myeloma* / therapy
  • Receptors, G-Protein-Coupled* / antagonists & inhibitors

Substances

  • Receptors, G-Protein-Coupled
  • GPRC5D protein, human
  • Immunoconjugates
  • Antibodies, Bispecific