Cord Blood Cells Used To Recreate a Functional Human Immune System in Mice

Researchers at the Josep Carreras Leukaemia Research Institute have developed a new method to recreate a robust and functional human immune system in mice using mononuclear cells from the cord blood. This new kind of mice, that count with most of the human immune cell types with lower host-versus-graft disease, are a better experimental platform to study the subtle interactions between the immune system, cancer cells and the tumour microenvironment, in healthy conditions and in disease.

Immunity plays a central role in the fight against cancer. Many of the current immunotherapies aim at helping the patient’s immune system to better recognize cancer cells – by using engineered antibodies – or by simply providing it with new cells, pre-equipped to search and destroy cancer. Either way, what is paramount is a deep understanding of how the immune system works and confronts tumours.

Unfortunately, the immune system is way too complex to model it in vitro or in a computer simulation, and animal experimentation is still unavoidable. To this end, researchers have been using mice as a model organism for a long time. But not just any mice: to understand the human immune system, they build a brand-new model, using cord blood human cells, into mice with no immune system of their own.

Current methods are quite inefficient in the sense that they are either too slow or at higher risk of developing graft-versus-host disease – the transplanted immune cells attacking mice tissues – a life-threatening condition for the recipient mice. To avoid these issues, a team from the Josep Carreras Leukaemia Research Institute, spearheaded by Dr. Carla Panisello and supervised by Dr. Pablo Menéndez and Dr. Clara Bueno, have developed a new method based on human cord blood mononuclear cells. Their findings have been recently published at the prestigious Journal for ImmunoTherapy of Cancer.

This new experimental platform showed a superior ability to produce and sustain a balanced immune cell population, accurately representing the lymphoid and the myeloid immune lines. Also, since cord blood cells are immunologically naïve - never been activated before – they tolerate mice structures much better, resulting in lowest rates of graft-versus-host disease.

Results confirmed that this new experimental model could deal with transplanted human hematologic and solid cancer cells much better than non-modified mice, with larger survival rates and a higher infiltration of immune cells into the tumours, mimicking a realistic immune response.

While these are just the first steps into this new experimental model, current results indicate that it could be a very promising system to better understand the inner workings of the immune system when facing cancer and develop new generations of immunotherapy, at the preclinical stage.

This research has been partly funded by grants from La Caixa Foundation, the European Union, the European Research Council, the Agencia Estatal de Investigación, the Instituto de Salud Carlos III, the Merck Foundation and the International Josep Carreras Foundation. No generative AI tools have been used in the production of this manuscript.

Reference: Panisello C, Aschero R, Martinez-Moreno A, et al. NSGS mice humanized with cord blood mononuclear cells show sustained and functional myeloid–lymphoid representation with limited graft-versus-host disease. J Immunother Cancer. 2024;12(10):e009198. doi: 10.1136/jitc-2024-009198

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