The Kidney Foundation of Canada

Dr. Nicoletta Eliopoulos 

Dr. Nicoletta Eliopoulos

McGill University, QC

Treatment of renal cell carcinoma using gene-modified mesenchymal stem cells


2018-2020:  $100,000 |  Biomedical Research Grants  |  Category: Cancer

Lay Summary

Kidney cancer is among the 15 most common cancers in men and women worldwide, with an incidence of about 338,000 new cases and 144,000 deaths yearly, the highest rates being in North America, Europe and Australia/New Zealand. In Canada, kidney cancer is the 10th most frequently arising cancer, with more than one quarter of cases being diagnosed at stage 4 when it is fatal for most patients. 80-90% of kidney cancers are renal cell carcinoma (RCC).

PTEN, (phosphatase and tensin homologue deleted on chromosome ten), is a tumor suppressor that is absent or reduced in many advanced cancers which include kidney cancer. PTEN levels are frequently decreased in advanced RCC, and this is associated with tumor progression and poor outcome. A variant of PTEN, named PTEN-Long, is capable of being released from cells and penetrating into other cells. Like PTEN, PTEN-Long also has anti-tumor actions. Injection of the PTEN-Long protein in mice with RCC, led to tumor regression, suggesting the potential of recombinant PTEN-Long protein as a treatment strategy. However, recombinant protein use in patients has several disadvantages. An alternative is to use mesenchymal stem cells, (MSCs), a type of adult stem cell, as a cellular vehicle for delivering PTEN-Long.

The main goal of our research is to determine if MSCs genetically modified to produce PTEN-Long can be used to combat kidney cancer. Our specific aims are to: (1) Determine if human MSCs from fat can be genetically modified to produce PTEN-Long and reveal its effects on human RCC cells in culture; (2) Evaluate in mice with RCC if administration of MSCs producing PTEN-Long leads to anti-tumor effects; (3) Reveal the location and duration of these MSCs following their administration in mice.

Our proposed research is very promising. The use of the easily isolated fat-derived MSCs to deliver PTEN-Long is intended to permit clinically relevant production of PTEN-Long and its various antitumor effects to effectively combat RCC (locally and at metastatic sites), aiming for a curative response and therefore relevant to the mission of the KFOC. Our study is novel, as it will be the first to evaluate the delivery of PTEN-Long by any cellular vehicle in any cancer model.

Biography

Dr. Nicoletta Eliopoulos is an Investigator at the Lady Davis Institute for Medical Research (LDI), Jewish General Hospital (JGH), and Assistant Professor in the Department of Surgery, Division of Surgical Research, at McGill University in Montreal. She is also the Laboratory Director of the JGH Cell Processing Center, a clinical-grade cell handling facility which is committed to fostering early-phase trials testing cell-based technologies.

Dr. Eliopoulos has a B.Sc. degree in Physiology from McGill University, M.Sc. and Ph.D. degrees in Pharmacology from the Université de Montréal, and received her postdoctoral training at the LDI in the laboratory of Dr. Jacques Galipeau.

Dr. Eliopoulos is a scientist with expertise in stem/progenitor cells for cell and gene therapy of various diseases, such as kidney injury and cancer. Her research laboratory currently performs studies on the pre-treatment, gene-enhancement and therapeutic use of mesenchymal stem cells (MSCs). She is very grateful to the Kidney Foundation of Canada for supporting her research exploring the use of gene-enhanced MSCs for the treatment of renal cell carcinoma.