Related Experiment Video
Updated: Oct 15, 2025
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
Development of a novel humanized mouse model for improved evaluation of in vivo anti-cancer effects of anti-PD-1
Ikumi Katano1, Asami Hanazawa1, Iyo Otsuka1
1Laboratory Animal Research Department, Central Institute for Experimental Animals, 3-25-12 Tono-machi, kawasaki-ku, Kawasaki, 210-0821, Japan.
Abstract:
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer in the clinic. Further discovery of novel drugs or therapeutic protocols that enhance efficacy requires reliable animal models that recapitulate human immune responses to ICI treatment in vivo. In this study, we utilized an immunodeficient NOG mouse substrain deficient for mouse FcγR genes, NOG-FcγR-/- mice, to evaluate the anti-cancer effects of nivolumab, an anti-programmed cell death-1 (PD-1) antibody. After reconstitution of human immune systems by human hematopoietic stem cell transplantation (huNOG-FcγR-/- mice), four different programmed death-ligand 1 (PD-L1)-positive human cancer cell lines were tested. Among them, the growth of three cell lines was strongly suppressed by nivolumab in huNOG-FcγR-/- mice, but not in conventional huNOG mice. Accordingly, immunohistochemistry demonstrated the enhanced infiltration of human T cells into tumor parenchyma in only nivolumab-treated huNOG-FcγR-/- mice. Consistently, the number of human T cells was increased in the spleen in huNOG-FcγR-/- mice by nivolumab but not in huNOG mice. Furthermore, human PD-L1 expression was strongly induced in the spleen of huNOG-FcγR-/- mice. Collectively, our results suggest that the anti-cancer effects of anti-PD-1 antibodies can be detected more clearly in NOG-FcγR-/- mice than in NOG mice.
Insights
New NOG-FcγR-/- mice enhance the detection of anti-cancer effects from immune checkpoint inhibitors like nivolumab. These mice better model human immune responses to programmed cell death-1 (PD-1) therapies.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer therapy.
- Developing novel ICI drugs requires accurate animal models reflecting human immune responses.
- NOG mice are commonly used but may not fully capture ICI efficacy.
Purpose of the Study:
- To evaluate the anti-cancer efficacy of nivolumab (an anti-PD-1 antibody) in a novel NOG mouse model lacking FcγR genes (NOG-FcγR-/-).
- To assess if this model enhances the detection of ICI therapeutic effects compared to conventional NOG mice.
Main Methods:
- Humanized NOG-FcγR-/- mice were generated via hematopoietic stem cell transplantation.
- Four human cancer cell lines (PD-L1 positive) were implanted.
- Tumor growth, T cell infiltration, and PD-L1 expression were analyzed after nivolumab treatment.
Main Results:
- Nivolumab significantly suppressed the growth of three out of four cancer cell lines in humanized NOG-FcγR-/- mice.
- Enhanced human T cell infiltration into tumors was observed in treated NOG-FcγR-/- mice.
- Increased T cell numbers and PD-L1 expression were noted in the spleen of treated NOG-FcγR-/- mice, but not in conventional NOG mice.
Conclusions:
- NOG-FcγR-/- mice demonstrate improved sensitivity for detecting the anti-cancer effects of anti-PD-1 antibodies.
- This model offers a more reliable platform for evaluating ICI therapies and understanding human anti-tumor immune responses in vivo.
