Humanized mouse model supports development, function, and tissue residency of human natural killer cells

Area of Science:

• Immunology
• Cancer Biology
• Translational Research

Background:

• Humanized mice are valuable for disease modeling but have limitations in human immune cell development.
• Insufficient development of human natural killer (NK) and T cells restricts their use in cancer research.

Purpose of the Study:

• To develop an improved humanized mouse model for studying human immune cell function in vivo.
• To enhance the development and function of human NK cells and T cells for cancer immunotherapy research.

Main Methods:

• Generation of a novel human IL15 and SIRPA knock-in mouse (SRG-15) on a Rag2 background.
• Transplantation of human hematopoietic stem and progenitor cells into SRG-15 mice.
• Analysis of human immune cell development, function, and tumor infiltration using mass cytometry and xenograft models.

Main Results:

• SRG-15 mice showed significantly improved development and functional maturation of human NK and CD8+ T cells.
• Human NK cell subsets in SRG-15 mice exhibited similar molecular profiles to those in humans.
• Human NK cells in SRG-15 mice effectively inhibited Burkitt's lymphoma xenograft growth after rituximab treatment.

Conclusions:

• The SRG-15 humanized mouse model supports robust development and function of human NK and T cells.
• This model is suitable for preclinical evaluation of NK cell-targeted cancer immunotherapies.
• SRG-15 mice facilitate the study of human antitumor immune responses in vivo.