A novel anti-CD146 antibody specifically targets cancer cells by internalizing the molecule

Marie Nollet (1, 2) , Jimmy Stalin (1, 2) , Anaïs Moyon (3, 1, 2) , Wael Traboulsi (1, 2) , Amel Essaadi (1, 2) , Stéphane Robert (1, 2) , Nausicaa Malissen (4) , Richard Bachelier (1, 2) , Laurent Daniel (5) , Alexandrine Foucault-Bertaud (1, 2) , Caroline Gaudy-Marqueste (6) , Romaric Lacroix (2, 1) , Aurélie S. Leroyer (1, 2) , Benjamin Guillet (1, 2) , Nathalie Bardin (1, 2) , Francoise Dignat-George (7, 1, 2) , Marcel Blot-Chabaud (1, 2)

1 VRCM - Vascular research center of Marseille
2 Physiopathologie de l'Endothelium
3 AMU PHARM - Aix-Marseille Université - Faculté de pharmacie
4 Département de dermatologie [CHU de Montpellier]
5 TIMONE - Hôpital de la Timone [CHU - APHM]
6 Département de dermatologie, CHU Marseille
7 Laboratoire d'Immunologie [Hôpital de la Conception - APHM]

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. www.impactjournals.com/oncotarget/

Keywords: PET; cancer; therapy; antibody; CD146

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Human health and pathology

Marie Nollet, Jimmy Stalin, Anaïs Moyon, Wael Traboulsi, Amel Essaadi, et al.. A novel anti-CD146 antibody specifically targets cancer cells by internalizing the molecule. Oncotarget, 2017, 8 (68), pp.112283 - 112296. ⟨10.18632/oncotarget.22736⟩. ⟨hal-01766676⟩