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Targeting cancer using evolutionary refined pathogen derived antigens (MalOnco)
Date du début: 1 sept. 2014, Date de fin: 31 août 2019 PROJET  TERMINÉ 

We have recently discovered a malaria protein which has shown a high potential in cancer treatment. In pregnant women, malaria infected red blood cells express a protein that binds to a distinct carbohydrate structure present only on cells of the maternal side of the placental circulation, but not elsewhere in the vasculature. This highly evolved binding system enables the parasite to evade clearance and infect placental tissue, causing pregnancy-associated malaria. This malaria protein binds to most cancer cells with a highly specific and strong interaction. It is apparent that cancer cells commonly express this modified glycoprotein, also found on placental cells, but rarely on normal somatic cells. The carbohydrate structures enable cancer cells to migrate and invade surrounding normal tissue, and to play a role in metastatic spread of the primary lesion.I have preliminary data showing that (1) the malaria protein binds specifically to a wide range of cancer cells and patient cancer tissues including melanoma, lymphoma, carcinomas and sarcomas, whereas no binding is detected to normal healthy cells or tissue, and (2) cancer cells treated with the malaria protein have markedly reduced growth and migration capacity.This raises the intriguing possibility that we can use this naturally refined parasite-host interaction mechanism as a tool to specifically target cancer and inhibit the metastatic potential. Furthermore, as the malaria protein binds strongly to patient-derived cancer tissues, the malaria protein could be used to differentiate between specific subtypes of cancers and possibly advance the diagnostic process in clinical settings. The proposed project augments a novel strategy of targeting a wide range of receptors involved in human disease using pathogen derived evolutionary refined ligands. I expect this project to pioneer the use of inherently refined parasite-host interactions as a tool to combat human malignant disease.

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