A novel anti-CD146 antibody specifically targets cancer cells by internalizing the molecule
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Marie Nollet1, Jimmy Stalin1, Anaïs Moyon1,2, Waël Traboulsi1, Amel Essaadi1, Stéphane Robert1, Nausicaa Malissen3, Richard Bachelier1, Laurent Daniel4, Alexandrine Foucault-Bertaud1, Caroline Gaudy-Marqueste3, Romaric Lacroix1, Aurélie S. Leroyer1, Benjamin Guillet1,2, Nathalie Bardin1, Françoise Dignat-George1 and Marcel Blot-Chabaud1
1INSERM UMR-S 1076, Aix-Marseille University, UFR Pharmacy, Marseille, France
2CERIMED, European Center of Research in Medical Imaging, Aix-Marseille University, Marseille, France
3Department of Dermatology, Timone Hospital, Assistance Publique des Hôpitaux de Marseille, Inserm UMR-S 911, Aix-Marseille University, Marseille, France
4Service d'anatomie Pathologique, Aix-Marseille University, Timone Hospital, Marseille, France
Marcel Blot-Chabaud, email: email@example.com
Keywords: antibody; CD146; cancer; PET; therapy
Received: July 20, 2017 Accepted: November 14, 2017 Published: November 28, 2017
CD146 is an adhesion molecule present on many tumors (melanoma, kidney, pancreas, breast, ...). In addition, it has been shown to be expressed on vascular endothelial and smooth muscle cells. Generating an antibody able to specifically recognize CD146 in cancer cells (designated as tumor CD146), but not in normal cells, would thus be of major interest for targeting tumor CD146 without affecting the vascular system.
We thus generated antibodies against the extracellular domain of the molecule produced in cancer cells and selected an antibody that specifically recognizes tumor CD146. This antibody (TsCD146 mAb) was able to detect CD146-positive tumors in human biopsies and in vivo, by PET imaging, in a murine xenograft model. In addition, TsCD146 mAb antibody was able to specifically detect CD146-positive cancer microparticles in the plasma of patients. TsCD146 mAb displayed also therapeutic effects since it was able to reduce the growth of human CD146-positive cancer cells xenografted in nude mice. This effect was due to a decrease in the proliferation and an increase in the apoptosis of CD146-positive cancer cells after TsCD146-mediated internalization of the cell surface CD146.
Thus, TsCD146 mAb could be of major interest for diagnostic and therapeutic strategies against CD146-positive tumors in a context of personalized medicine.
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