CORPORATE

A revolution is taking place in cancer detection and treatment research.

L-glucose is the mirror-image isomer of naturally occurring glucose (D-glucose). It has been a long belief that mammalian cells take in and metabolize only D-glucose, and not L-glucose. In 2010, a researcher in Hirosaki University found that a fluorophore-conjugating L-glucose compound 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-L-glucose (2-NBDLG) is taken up into tumor cells expressing a malignant feature in a highly selective manner. His group soon noticed that the L-glucose moiety is essential for the uptake. The L-glucose uptake has been detected not only in divergent tumor cell lines such as a pancreatic tumor (Sasaki, A. et al., Human Cell 29: 37-45, 2016) and a osteosarcoma (Ogawa, T. et al., Human Cell 34: 634-643, 2021), but also in non-cultured human biopsy/ascites/urine specimens that were freshly collected from patients of gastric cancer, ovarian cancer, uterine body cancer, and bladder cancer (Patents JP6406715, JP6670503, US10551387B2, EP3199638B1).

Detailed studies have further revealed that the L-glucose uptake was detected in tumor cells showing a mitochondrial dysfunction known as the Warburg effect (Ono K. et al. Cancers 2020). Taking advantage of this finding, ORBIO Corporation has been developing a high-precision cancer-detection technology that enables a single-cell cancer diagnosis to an unprecedented high stage (Patents JP6019500, EP2703495B1, ZL201280015126.5), revolutionizing conventional D-glucose methods such as positron emission tomography (PET) by [18F]2-fluoro-2-deoxy-D-glucose (FDG) (Gambhir, S. Nat. Rev. Cancer 2: 683-693, 2002) and liquid biopsy-based cell screening by 2-NBDG, a fluorescently labeled D-glucose (Yamada, K. et al., Nat. Protoc. 2: 753-762, 2007; Li, Z. et al., Nat. Commun. 10: 3856, 2019).

Furthermore, ORBIO Corporation has applied the outstanding cancer cell-selectivity of L-glucose to the investigation of anti-cancer drugs minimizing adverse side effects. Personalized cancer medicine today faces individual complexities including diversity in protein expressions and gene mutations. The treatment using L-glucose is an approach from a different angle, a nutrient that a wide spectrum of rapidly proliferating malignant cells may take in regardless of their phenotypes/genotypes.

Based on this strategy, ORBIO Corporation is developing CLG (Patents, JP6566348, US10001487B2, US10509041B2, EP3130596B1) and such as ALG (Patent JP6982358), promising candidate molecules for anti-cancer drugs having an excellent cancer selectivity that has never been expected before.

ORBIO is developing a single cell therapy using L-glucose as a drug delivery system (DDS) especially focusing on the treatment of malignant neuroendocrine neoplasm, in particular, insulinoma as the initial target, then refractory cancers including pancreatic cancer, biliary tract cancer, and ovarian cancer, as well as sarcoma/osteosarcoma with poor prognosis. Since CLG and 2-NBDLG are taken up into the same tumor cells through the same phloretin-inhibitable mechanism (Patents, JP6566348, US10001487B2, US10509041B2, EP3130596B1), 2-NBDLG will be effectively utilized as an in vitro diagnostic biomarker for CLG.