GPRC5D Specific Neutra™ Antibody Products

G protein-coupled receptor class C group 5 member D (GPRC5D) is a cell surface receptor protein involved in various cellular signaling pathways. It is coded by the GPRC5D gene located on chromosome 12 in humans and consists of a seven-transmembrane domain characteristic of G protein-coupled receptors (GPCRs). GPRC5D is primarily expressed in the respiratory epithelium and is vital in regulating cell proliferation, differentiation, and apoptosis. Additionally, it has been implicated in the pathogenesis of multiple myeloma (MM), making it a potential therapeutic target.

Its Gene ID: 55507, UniProtKB ID: Q9NZD1, and OMIM ID: 607437.

Fig.1 Structure of GPRC5D.¹

GPRC5D Expression in Normal Tissue

GPRC5D is mainly expressed on epithelium structures, including hair follicles, skin, eccrine glands and the base of filiform papillae on the tongue. GPRC5D protein has also been detected in immune cells with plasma cell characteristics. However, GPRC5D is not expressed in normal T cells, B cells, monocytes, and bone marrow progenitors. GPRC5D expression is also suspected to exist in the human nailbed. Furthermore, in the central nervous system's motor neurons of the brainstem, researchers have discovered low levels of GPRC5D.

GPRC5D in Multiple Myeloma

GPRC5D has emerged as a promising target in MM due to its selective and high expression on malignant plasma cells. Studies have shown that GPRC5D is significantly expressed in MM cells, and is prevalent in the bone marrow of people with MM and smoldering MM. Furthermore, mRNA expression of GPRC5D is higher in MM cells than in other hematologic malignancies. Increased GPRC5D mRNA expression from MM cells, due to the high proportions of malignant plasma cells, is linked to a variety of genetic abnormalities and high-risk illnesses. In bone marrow, the increased expression of GPRC5D mRNA has been linked to poor prognosis and disease results. Targeting GPRC5D with antibodies has shown encouraging results in preclinical models and early-phase clinical trials, demonstrating the potential for precision therapy in MM.

Antibodies Targeting GPRC5D

The treatment of MM using GPRC5D bispecific antibodies has shown promising results. Bispecific antibodies targeting GPRC5D and CD3 have demonstrated potent anti-tumor activity by redirecting T cells to kill GPRC5D-expressing myeloma cells. Clinical trials have shown encouraging efficacy and manageable safety outcomes for patients in the relapsed/refractory stage. Additionally, other bispecific antibodies are being investigated for their ability to induce robust T cell-mediated cytotoxicity against GPRC5D-positive cancer cells. These advancements highlight GPRC5D-targeting antibodies as a promising therapeutic strategy for MM.

Fig.2 A generalized structure of bispecific antibodies targeting GPRC5D and CD3.¹

Creative Biolabs offers anti-GPRC5D antibody products that are recombinantly expressed.

REFERENCE

1. Rodriguez-Otero, Paula, et al. "GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review." Blood Cancer Journal 14.1 (2024): 24. Distributed under Open Access license CC BY 4.0, without modification.