(Oncodesign) 免疫腫瘍学におけるヒト化マウス：前臨床研究のゲームチェンジャー

要旨

Immune cells within the tumor microenvironment are now well recognized as targets of interest for cancer treatment.

Many findings from conventional animal models do not apply to humans due to intrinsic differences between species. This fact would explain the great need for humanized mouse models that will accurately support the preclinical development of such therapeutic approaches.

Human immune system should be reconstituted in immunodeficient mice using either human PBMCs, hematopoietic stem cells (HSCs) or other differentiated cells such as T and NK cells. So called “Humanized Immune System” (HIS) mouse models, have been established to study the complex interaction of the human immune system during human disorders, when the syngeneic mouse model cannot constitute the test model.

Humanized immunodeficient mice, bearing human immune cells with human target tumor cells, are relevant models to test various therapeutic strategies (e.g. adoptive cell transfer, immune checkpoint inhibitors, oncolytic viruses…) in oncology.

Therapeutic efficiency was assessed by monitoring mice survival and tumor growth using caliper or imaging. The impact of therapeutics on tumors and immune cells was also assessed by flow cytometry and immunohistochemistry analyses.