MONTREAL, January 24, 2022 – A research team led by Professor Christian Beauséjour of CHU Sainte-Justine and Université de Montréal has developed a novel approach to studying human cancers in mice. The approach simulates, in an animal model, the interaction between cancer and immune cells in order to obtain a more accurate picture of that patient’s response to treatment.

Published in Cell Reports Methods, the results of this work point the way to new cancer therapies. 

“Humanized” mice

For over two decades, advances in oncology have been made possible largely through humanized mice. This laboratory-designed animal model, where human pathologies are “injected” into a mouse that has no immune system, makes it possible to test drugs intended for humans.

“The drawback is that this approach doesn’t provide an environment where human tumours are confronted with autologous immune cells, because the mice are immunodeficient,” explains Professor Beauséjour, a researcher at CHU Sainte-Justine and professor in the Department of Pharmacology and Physiology at the Université de Montréal. “This makes it difficult to obtain accurate data on the efficacy of immunotherapies, one of the reasons very few drugs reach the final stages of approval.” 

Healthy patients to the rescue

“Through the use of healthy donor-derived stem cells, we recreate human tumours that are transplanted into autologous humanized mice – that is, the mice are injected with white blood cells that are from the same donor as the tumour – to simulate an immune microenvironment,” says Gaël Moquin-Beaudry, first author of the study and a PhD graduate from the Department of Pharmacology and Physiology at the Université de Montréal.

“The beauty of this approach is the almost unlimited access to peripheral blood and its immune cell components,” adds Gaël Moquin-Beaudry. “It’s also possible to generate a multitude of cancers. For example, one only has to differentiate a healthy stem cell into cells of neural origin to then transform them into a brain tumour.” 

In collaboration with the laboratories of Dr. Massimilliano Paganelli and Dr. Elie Haddad at CHU Sainte-Justine, the research team demonstrated that fibroblastic, hepatic and neural tumours were all efficiently infiltrated and partially or totally rejected by autologous immune cells in humanized mice. This finding validates the immense potential of this innovative approach.

The future of research

The recognition that the immune system plays a role in cancer has led the industry to develop numerous promising immunotherapies. However, the success rate of moving from Phase I to regulatory approval and to clinical practice remains very low.

“If we increase the success rate in preclinical stages, this will translate into significant benefits for patients and also reduce drug production costs,” concludes Gaël Moquin-Beaudry.

About this study

The article “Autologous humanized mouse models of iPSC-derived tumors allow for the evaluation and modulation of cancer-immune cell interactions,” written by Gaël Moquin-Beaudry et al, was published in January 2022 in Cell Reports Methods. The study was funded by the Fondation Charles Bruneau, the Canadian Institutes of Health Research and the Fonds de recherche du Québec – Santé.

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