GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells
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GPRC5D is an attractive target for immunotherapy of myeloma, and optimized GPRC5D-targeted CAR T cells eradicate myeloma xenografts.
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GPRC5D is highly expressed in malignant bone marrow plasma cells from CD138+ multiple myeloma patients, its expression in normal tissues is primarily limited to the hair follicle region, and it is expressed independently of BCMA.
“GPRC5D (G protein-coupled receptor, class C, group 5, member D) is a G-protein-coupled orphan receptor that highly expressed in malignant bone marrow plasma cells from CD138+ MM patients. Its expression in normal tissues is primarily limited to the hair follicle region. Importantly, GPRC5D is expressed independently of BCMA, making it a promising target for multiple myeloma therapy [214, 215].”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [214]
GPRC5D has shown independent expression from BCMA and has demonstrated excellent anti-tumor activity in MM models with BCMA loss.
“One such promising target is GPRC5D, which has shown independent expression from BCMA and has demonstrated excellent anti-tumor activity in MM models with BCMA loss.”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [214]
GPRC5D expression is associated with markers of high-risk myeloma.
“GPRC5D expression is enriched in malignant plasma cells and is associated with markers of high-risk myeloma. 13,14,16,19-21”
From Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma (2022) · cites this paper as [16]
GPRC5D expression is enriched in malignant plasma cells.
“GPRC5D expression is enriched in malignant plasma cells and is associated with markers of high-risk myeloma. 13,14,16,19-21”
From Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma (2022) · cites this paper as [16]
GPRC5D is expressed in nail beds in mice.
“Given the localized expression of GPRC5D in nail beds in mice, 15-17”
From Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma (2022) · cites this paper as [16]
Nail toxic effects are probably related to on-target talquetamab activity.
“Given the localized expression of GPRC5D in nail beds in mice, 15-17 nail toxic effects are probably related to on-target talquetamab activity.”
From Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma (2022) · cites this paper as [16]
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- Authors
- Smith, E. L., Harrington, K., Staehr, M., Masakayan, R., Jones, J., Long, T. J., Ng, K. Y., Ghoddusi, M., Purdon, T. J., Wang, X., Do, T., Pham, M. T., Brown, J. M., De Larrea, C. F., Olson, E., Peguero, E., Wang, P., Liu, H., Xu, Y., Garrett-Thomson, S. C., Almo, S. C., Wendel, H.-G., Riviere, I., Liu, C., Sather, B., & Brentjens, R. J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Juno Therapeutics (United States) (US)
- Cellular Therapeutics Center, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
- Sloan Kettering Institute, New York, NY 10065, USA.
- Eureka Therapeutics (United States) (US)
- Albert Einstein College of Medicine (US)
- Cell Therapy and Cell Engineering Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
- Eureka Therapeutics, Emeryville, CA 94608, USA.
- Corresponding author
- Brentjens, Renier J.
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2019-03-27
- Volume
- 11
- Issue
- 485
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC7508042
- OpenAlex
- W2923396001
- Cited by
- 391
- References
- 35
- Citations by year
- 2026: 31 · 2025: 55 · 2024: 79 · 2023: 68 · 2022: 46 · 2021: 55 · 2020: 42 · 2019: 14
- FWCI
- 16.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 CA198095, R01 HG008325)
- National Cancer Institute (P30 CA008748, U54 OD020355-01, PO1 CA190174-01, P01 CA059350, P30 CA013330, R01 CA138738-05)
- Multiple Myeloma Research Foundation
- American Society of Hematology
- Leukemia and Lymphoma Society
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- GPRC5D, multiple myeloma, CAR T-cell therapy, BCMA, scFv, phage display
- MeSH terms
- Receptors, Chimeric Antigen, Animals, Antibody Specificity, Humans, Multiple Myeloma, RNA, Messenger, Gene Expression, Immunotherapy, Adoptive, Mice, SCID, Mice, Inbred NOD, Xenograft Model Antitumor Assays, Receptors, G-Protein-Coupled, Cell Line, Tumor, Mice, B-Cell Maturation Antigen, Single-Chain Antibodies, Translational Research, Biomedical
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