The GPNMB gene encodes a type I transmembrane glycoprotein known to be regulated by the microphthalmia-associated transcription factor (MiTF) family.
Researchers at the University of Calgary have demonstrated that GPNMB has high and homogenous expression across cancers with deregulated MiTF activity, including subtypes of sarcoma and renal cell carcinoma. Additionally, high levels of GPNMB expression have been demonstrated in triple-negative breast cancer (TNBC) and tumour-associated macrophages across cancers. These researchers have developed a Chimeric Antigen Receptor (CAR) targeting GPNMB that, when expressed in T cells, efficiently kills GPNMB-expressing cancer cells grown in culture and mice.
Notably, GPNMB has been safely targeted with an antibody-drug conjugate in breast cancer, lung cancer, melanoma, and osteosarcoma.
AREAS OF APPLICATION
- Tumor elimination
- Extensively tested in preclinical models of primary and metastatic disease: significant CAR T expansion and complete and durable tumor elimination in preclinical models.
- GPNMB is a clinically tested, safety proven immunotherapy target.
- Phase 1 clinical trial (funding secured) in sarcoma, renal cell cancer, and breast cancer commences in 2023/2024.
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