Review
. 2026 Sep 1;132(17):e70597.
doi: 10.1002/cncr.70597.
Affiliations
Expand
Affiliation
1 Department of Medicine, University of California, San Francisco, California, USA.
Item in Clipboard
Review
Darren Pan et al.
Cancer.
2026.
Show details
Display options
Display options
Format
Abstract
PubMed
PMID
. 2026 Sep 1;132(17):e70597.
doi: 10.1002/cncr.70597.
Affiliation
1 Department of Medicine, University of California, San Francisco, California, USA.
Item in Clipboard
CiteDisplay options
Display options
Format
AbstractPubMedPMID
Abstract
G-protein-coupled receptor class C group 5 member D (GPRC5D) has emerged as a crucial immunotherapy target in relapsed/refractory multiple myeloma. Although the T-cell-engaging bispecific antibody talquetamab is currently the only approved anti-GPRC5D therapy, numerous promising agents are undergoing clinical evaluation. While anti-GPRC5D chimeric antigen receptor T cells show potential, this review focuses specifically on T-cell-engaging bispecific and trispecific antibodies. We highlight how GPRC5D differs clinically from B-cell maturation antigen, explore mechanisms of resistance, discuss novel therapeutic strategies including combination regimens and talquetamab as bridging therapy to chimeric antigen receptor T cells, and review key investigational T-cell engagers currently in development.
Keywords:
CAR‐T cells; GPRC5D; T‐cell engagers; bridging; combination therapy; immunotherapy; relapsed refractory multiple myeloma.
© 2026 American Cancer Society. All rights reserved, including rights for text and data mining and training of artificial intelligence technologies or similar technologies.
References
Rodriguez‐Otero P, van de Donk NW, Pillarisetti K, et al. GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review. Blood Cancer J. 2024;14(1):24. doi:10.1038/s41408‐023‐00966‐9
Li J, Stagg NJ, Johnston J, et al. Membrane‐proximal epitope facilitates efficient T cell synapse formation by anti‐FcRH5/CD3 and is a requirement for myeloma cell killing. Cancer Cell. 2017;31(3):383‐395. doi:10.1016/j.ccell.2017.02.001
Pillarisetti K, Edavettal S, Mendonça M, et al. A T‐cell–redirecting bispecific G‐protein–coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. Blood. 2020;135(15):1232‐1243. doi:10.1182/blood.2019003342
Atamaniuk J, Gleiss A, Porpaczy E, et al. Overexpression of G protein‐coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma. Eur J Clin Invest. 2012;42(9):953‐960. doi:10.1111/j.1365‐2362.2012.02679.x
Cohen Y, Gutwein O, Garach‐Jehoshua O, Bar‐Haim A, Kornberg A. GPRC5D is a promising marker for monitoring the tumor load and to target multiple myeloma cells. Hematology. 2013;18(6):348‐351. doi:10.1179/1607845413y.0000000079
Show all 60 references
MeSH terms
Antibodies, Bispecific* / pharmacology
Antibodies, Bispecific* / therapeutic use
Multiple Myeloma* / drug therapy
Multiple Myeloma* / immunology
Multiple Myeloma* / therapy
Receptors, G-Protein-Coupled* / antagonists & inhibitors
Receptors, G-Protein-Coupled* / immunology
T-Lymphocytes / immunology
Substances
Receptors, G-Protein-Coupled
[x]
Cite
Copy
Format:
AMA
APA
MLA
NLM