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Targeting cancer using evolutionary refined pathogen derived antigens

Final Report Summary - MALONCO (Targeting cancer using evolutionary refined pathogen derived antigens)

The MalOnco project supported through an ERC CoG we made the groundbreaking discovery that distinct Chondroitin Sulfate (CS) carbohydrates, normally expressed only during fetal and placental development, are also present in high amounts on the surface of most tumor cells. We have named these distinct carbohydrates onco-fetal CS. An evolutionary refined malaria protein (VAR2) binds to ofCS with very high affinity and specificity and could thus be used to specifically target ofCS in cancer. Throughout MalOnco we demonstrated that VAR2 binds to the vast majority of human cancers, and that upon intra venous injection of VAR2 in tumor bearing animals, the protein locates specifically to the tumor tissue. When armed with a cellular toxin, the VAR2 effectivally eradicates the solid primary tumors as well as metastasis. A key result of the project was the demonstration of a pivotal role of ofCS in cancer cell migration and metastasis formation and the demonstration that the VAR2 protein can be used to capture circulating tumor cells in transit in the blood of cancer patients. All together the results of MalOnco raises the hope for the development of a novel cancer targeting therapy, also effective against tumors with no current treatment possibilities. And the capacity of VAR2 technology to effectively capture circulating tumor cells raises the intriguing possibility of developing an early and broad cancer diagnostic tool.