GPRC5D as a Novel Immunotherapeutic Target in Multiple Myeloma

After the popular targets CD38 and BCMA for the treatment of multiple myeloma (MM), GPRC5D has become an entirely new target. GPRC5D has shown very positive results in early clinical trials for the treatment of multiple myeloma patients. With excellent clinical efficacy, GPRC5D stands out as a new potential target for the treatment of MM.

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Introduction of GPRC5D

GPRC5D (G protein-coupled receptor, class C, group 5, member D) is a member of the family of G protein-coupled receptors (GPCRs) and is an orphan 7-channel transmembrane receptor protein. In recent years, GPCRs are emerging as important drug targets for drug discovery. To date, nearly 2,000 G protein-coupled receptors have been reported, which are the most widely distributed and important membrane protein receptors in the human body. GPRC5D, as a novel GPCR drug target, has no endogenous ligand found for the time being and belongs to an orphan receptor.GPRC5D is widely expressed in malignant bone marrow plasma cells, hair follicles, and lungs, whereas in normal tissues, it is expressed to a small extent or is not expressed. Studies have shown that GPRC5D is specifically highly expressed in patients with multiple myeloma (MM). Therefore, GPRC5D, as a key new target in MM therapy, has attracted great attention from researchers as well as pharmaceutical companies. Currently, several drugs targeting GPRC5D or GPRC5D-based combinations are in clinical development. These newly developed target drugs are mainly used for multiple myeloma MM treatment. Thus, GPRC5D is expected to be the next ideal target for the treatment of MM.

Introduction of Multiple Myeloma (MM)

Multiple myeloma MM is a cancer of plasma cells. Plasma cells are found in the bone marrow and are an important part of the immune system. When a malignant proliferation of plasma cells occurs in the bone marrow, it will lead to multiple myeloma MM. As a serious hematologic disease, MM can destroy the bones and the immune system, and its clinical manifestations are highly variable, such as bone pain, osteoporosis, renal lesions, inflammation of the lungs, and hypercalcemia, among others. Currently, there is a large unmet clinical need for multiple myeloma, especially for relapsed patients with low BCMA expression or BCMA-negative associated relapses, for which no better treatment strategy has been developed. However, with the emergence of emerging immune target molecules, researchers have set their sights on a new target of the GPCRs family-GPRC5D.

GPRC5D Therapeutic Strategy in Multiple Myeloma (MM)

In recent years, there have been significant advances in targeted therapies for multiple myeloma MM, mainly including immunomodulators, proteasome inhibitors, monoclonal antibodies, and chimeric antigen receptor cell (CAR-T) therapies. Although front-line therapy has achieved good efficacy, multi-line therapy is very limited. Excitingly, it was found that GPRC5D is independently expressed with BCMA, which means that GPRC5D can be either singly targeted or dual-targeted for therapeutic drug development. This finding, which provides a new therapeutic pathway for multiple myeloma MM patients, makes the clinical value of GPRC5D prominent. Currently, therapeutic strategies for GPRC5D in multiple myeloma (MM) are focused on GPRC5D CAR-T cell therapy and bispecific antibody therapy in combination with GPRC5D.

Advances in GPRC5D-Related Drug Research

GPRC5D is a newly discovered target. Although existing studies and clinical pipeline are still relatively scarce, published clinical data demonstrate that GPRC5D has good efficacy and considerable potential in multiple myeloma (MM) treatment. Overall, although GPRC5D has not yet been marketed as an antibody drug or other therapeutic approach, and the clinical pipelines are all at a relatively early stage, GPRC5D is specifically and highly expressed on MM cells, and clinical data have confirmed that the GPRC5D target itself has excellent efficacy. Especially in the model of tumor recurrence due to BCMA antigen loss, it was shown that GPRC5D-targeted CAR T cells have anti-tumor activity, and GPRC5D would be a better specific MM target in alleviating the problem of BCMA escape-mediated recurrence. Targeting GPRC5D will have the potential to enhance the inadequacy of existing BCMA-only bispecific antibody and T-cell therapies and improve the long-term clinical benefit for multiple myeloma patients.

GPRC5D Related Products & Applications

Creative Biogene is committed to providing our customers with innovative research tools and resources to explore the functions and applications of GPRC5D. We specialize in transfected stable cell lines, preformed viral particles and virus-like particles (VLPs) to provide comprehensive solutions for studying GPRC5D-related processes.

Transfected stable cell lines

Our transfected stable cell lines express GPRC5D or its variants, providing a reliable and consistent cellular model for investigating GPRC5D function, signaling pathways, and drug responses. These cell lines serve as invaluable tools for studying the role of GPRC5D in cancer biology, cellular signaling, and other relevant research areas.

Cat.No.	Product Name	Price
CSC-DC006607	Panoply™ Human GPRC5D Knockdown Stable Cell Line	Inquiry
CSC-RG1812	Human GPRC5D Stable Cell Line - MC38	Inquiry
CSC-RG1816	Human GPRC5D Stable Cell Line - CT26	Inquiry
CSC-RG1817	Monkey GPRC5D Stable Cell Line - HEK293T	Inquiry
CSC-RG1818	Mouse Gprc5d Stable Cell Line - HEK293T	Inquiry
CSC-RG1819	Human GPRC5D Stable Cell Line - HEK293T	Inquiry
CSC-RG1820	Human GPRC5D Stable Cell Line - CHO-K1	Inquiry
CSC-RG1837	Mouse Gprc5d Stable Cell Line-CHO-S	Inquiry
CSC-RG1842	Human GPRC5D Stable Cell Line - A20	Inquiry
CSC-RH0045M	Humanized GPRC5D Murine Tumor Cell Line	Inquiry
CSC-SC006607	Panoply™ Human GPRC5D Over-expressing Stable Cell Line	Inquiry

Premade viral particles

Our pre-made viral particles, such as lentiviral or adenoviral particles, contain GPRC5D genes or shRNA constructs designed to modulate GPRC5D expression. These particles offer an efficient and targeted approach to deliver GPRC5D-related genetic material into specific cell types. Researchers can utilize these particles to investigate GPRC5D function, assess its role in disease progression, or explore potential therapeutic interventions.

Cat.No.	Product Name	Price
AD07095Z	Human GPRC5D adenoviral particles	Inquiry
LV14042L	Human GPRC5D (NM_018654) lentivirus particles	Inquiry

Virus-like particles (VLPs)

Our GPRC5D-specific VLPs are synthetic structures that mimic the outer shell of a virus. This VLPs is engineered to display GPRC5D on their surface, allowing researchers to study GPRC5D interactions, signaling, and potential therapeutic applications. GPRC5D VLPs serve as valuable tools for immunological studies, vaccine development, drug discovery, and high-throughput screening.

Cat.No.	Product Name	Price
VLP-N-00025	Human GPRC5D Virus-Like Particles	Inquiry

Reference:

Pillarisetti, K.; et al. A T-cell–redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma. Blood, The Journal of the American Society of Hematology. 2020, 135(15): 1232-1243.

* For research use only. Not intended for any clinical use.

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