Impact of hMSCs on solid tumor growth in novel tumor/immune system humanized mice
Gaël Moquin-Beaudry1,2*, Cynthia Desaulniers-Langevin1,2, Basma Benabdallah1, Lina Palacio1,2, Christian Beauséjour1,2
1CHU Sainte-Justine Research Center, Montreal, Quebec, Canada, 2Pharmacology and Physiology Department, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada
Clinical trial approbation for novel solid tumor therapies have been steadily decreasing since the 1990s to reach barely 7% in recent years constituting considerable health and financial concerns that need to be addressed. We believe one of the reasons behind such worrying number is the lack of clinically relevant and accessible pre-clinical models notably for the study of the patient’s own immune system on tumor emergence, progression and elimination. To address this issue, we developed two unique, novel and flexible humanized tumor/immune system mouse models to study the implication of functional human immune cells in anti-cancer therapies. Briefly, primary fibroblasts are transformed into tumor cells by modification with defined proto-oncogenes (hTERT, RasV12, SV40ER) and injected into NSG mice humanized by either 1) adoptive transfer of peripheral blood mononucleated cells (PBMCs) allogenic or autologous to the fibroblasts (Hu-PBMC model) or 2) Bone marrow/Liver/thymus (BLT)-type reconstitution with fetal hematopoietic stem cells (Hu-BLT model). With these models, we are currently investigating the impact of human mesenchymal stromal cells (MSCs) on tumor growth in the presence of functional mature human immune cells in mice. Our preliminary results reveal that while allogenic tumors are efficiently rejected and show massive infiltrations with CD8 T cells, the systemic injection of 107 MSCs did not interfere significantly with tumor growth and had no impact on tumor infiltration despite their known immuno-modulatory properties in vitro. Autologous studies are currently underway. Overall, we believe the unique and versatile tumor/immune system mouse models that we generated will provide essential pre-clinical insight for the safe use of MSC-based cell therapies in humans.
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