31 Mai 2018

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Biologie / Santé



CD146 (also identified as MCAM, Mel-CAM, MUC18, Gicerin, S-endo1) is a transmembrane glycoprotein  initially discovered in human melanoma cells and was then described in many other tumors such as pancreas, kidney, prostate, lung or breast cancer. In cancer cells, CD146 is involved in tumor growth and dissemination, making it a promising pharmacological target.

Because CD146 is expressed both on cancer cells and endothelial cells, targeting membrane CD146 remains an hazardous challenge due to possible negative vascular effects. Therefore, no therapy targeting membrane CD146 has been developed so far.

The Tumor-specific CD146 (TsCD146 mAb) is a new monoclonal antibody specifically binding CD146 in cancer cells but not in normal cells.

With a high tumor affinity, TsCD146 mAb could be useful for diagnosing, stratifying and/or establishing the prognostic of a cancer:

TsCD146 mAb recognizes the tumor cells (e.g. melanoma, colon, kidney and pancreatic cancer cells) but not the endothelial cells nor the smooth muscle cells.
TsCD146 mAb is also able to detect CD146 in human biopsies of cancerous tissues but not in healthy tissues.
Radiolabeled TsCD146 mAb detects CD146-positive melanoma tumors in a xenograft mouse model.
TsCD146 mAb detects cancer cells microparticles in the plasma of melanoma patients and allows their quantification: the number of CD146-positive microparticles was significantly increased in metastatic patients versus patients with initial tumor
TsCD146 mAb is also a promising drug candidate for personalized treatment of CD146-positive cancer by targeting cancerous tissues without vascular effects:

TsCD146 mAb decreases the proliferation of tumors cells.
TsCD146 mAb reduces tumor growth of melanoma cells xenografted in nude mice: 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
Publication: A novel anti-CD146 antibody specifically targets cancer cells by internalizing the molecule.

Nollet et al, Oncotarget 2017

We are currently generating an antibody drug conjugate (ADC) by combining TsCD146 mAb and toxins and plan to realize in vitro studies on melanoma cell lines and in vivo studies in melanoma and renal cancer cells xenografted in mice.


Personalized diagnosis and therapy of tumors

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