On February 12, 2019 A team led by Dr. Chi-Huey Wong, Distinguished Research Fellow at Academia Sinica in Taiwan, in collaboration with OBI scientists, has demonstrated in a recent study that the Globo-series glycosphingolipids (GSLs) antigens: Globo-H, SSEA-3, and SSEA-4 are specifically expressed on cancer cells and are found to correlate with tumor survival (Press release, OBI Pharma, FEB 12, 2019, View Source [SID1234533318]). This finding supports the basis of the anti-Globo series pipeline under development by OBI Pharma Inc.
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The article entitled "Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer" was published ahead of print on February 11, 2019 in the Proceedings of the National Academy of Sciences (PNAS)[1]. The study indicates that the GSL antigens can form a complex in membrane lipid raft with protein kinases such as caveolin-1 (CAV1), AKT, FAK and RIP. The reaction can trigger signaling pathways and promote tumor survival.
The study revealed that the expression of b3GalT5 is up-regulated in breast cancer and is highly correlated with tumor progression and poor survival in patients. On the other hand, knockdown of b3GalT5 in breast cancer cells can induce tumor apoptosis. Synthesis of SSEA-3 requires the presence of b3GalT5. SSEA-3 is the precursor of SSEA-4 and Globo H. When the expression of b3GalT5 decreases, expression of SSEA-3 also decreases. Subsequently, expression of SSEA-4 and Globo H are reduced.
When GSL antigens are unavailable or dysfunctional, protein kinases such as CAV1, AKT, FAK and RIP cannot signal to promote tumor survival. OBI’s anti-Globo series pipeline, such as OBI-888 (Globo H mAb) and OBI-898 (SSEA-4 mAb), targets high Globo H and SSEA-4 expressing cancers, suppressing or removing Globo H and SSEA-4 antigens to trigger tumor apoptosis. This study supports the scientific basis for OBI’s anti-Globo series pipeline and use of antibodies against the GSL antigens in treatment of breast and solid tumor cancers.
[1] "Signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer." Proceedings of the National Academy of Sciences (PNAS), Published ahead of print February 11, 2019. View Source