Researchers have created an innovative technique to construct a strong and functional human immune system within mice, utilizing mononuclear cells derived from cord blood. These specially engineered mice possess a majority of the human immune cell types while experiencing reduced host-versus-graft disease, making them a superior experimental model for exploring the intricate interactions among the immune system, cancer cells, and the tumor microenvironment in both healthy and disease conditions.
The immune system is pivotal in combating cancer. Many modern immunotherapies focus on enhancing the patient’s immune response to better identify cancer cells, often through the use of modified antibodies or by introducing new, pre-prepared immune cells designed to target and eliminate cancer. Understanding the mechanisms of the immune system in its battle against tumors is crucial for developing these therapies.
Sadly, the immune system’s complexity makes it challenging to replicate in a laboratory or through computer models, which means animal testing remains essential. For this reason, scientists have long used mice as models. However, they specifically create new models utilizing human cord blood cells in mice that lack any immune system of their own to study human immune responses effectively.
Existing techniques have limitations; they are either too slow or carry a significant risk of triggering graft-versus-host disease, where the immune cells launched against the mouse’s tissues result in a life-threatening situation for the host. To tackle these challenges, a research team from the Josep Carreras Leukaemia Research Institute, led by Dr. Carla Panisello and guided by Dr. Pablo Menéndez and Dr. Clara Bueno, has devised a new approach using mononuclear cells from human cord blood. Their work has recently appeared in the Journal for ImmunoTherapy of Cancer.
This advanced experimental model demonstrated an improved capacity to generate and maintain a balanced immune cell population, closely mirroring both the lymphoid and myeloid immune lineages. Additionally, since the cord blood cells have never been previously activated, they integrate more smoothly with the mice’s structures, leading to lower occurrences of graft-versus-host disease.
The results showcased that this new experimental framework performed significantly better in dealing with transplanted human hematologic and solid tumor cells compared to conventional mice, exhibiting better survival rates and a more substantial infiltration of immune cells into the tumors, which reflects a more authentic immune response.
While these findings are merely the initial phases of this experimental model, they suggest substantial potential for enhancing our comprehension of the immune system’s functions in the context of cancer and for fostering the development of new immunotherapy strategies at the preclinical level.
This research received partial funding from La Caixa Foundation, the European Union, the European Research Council, the Agencia Estatal de Investigación, Instituto de Salud Carlos III, the Merck Foundation, and the International Josep Carreras Foundation. The manuscript was produced without the involvement of generative AI tools.
