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Updated: Feb 18, 2026
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy
Minan Wang1, Li-Chin Yao1, Mingshan Cheng1
1Department of In Vivo Pharmacology Services, The Jackson Laboratory, Sacramento, California, USA.
Abstract:
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, nonobese diabetic (NOD).Cg- PrkdcscidIL2rgtm1Wjl/Sz (null; NSG) mice were transplanted with human (h)CD34+ hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; non-small cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX). Tumor growth curves were similar in HuNSG compared with nonhuman immune-engrafted NSG mice. Treatment with pembrolizumab, which targets programmed cell death protein 1, produced significant growth inhibition in both CDX and PDX tumors in HuNSG but not in NSG mice. Finally, inhibition of tumor growth was dependent on hCD8+ T cells, as demonstrated by antibody-mediated depletion. Thus, tumor-bearing HuNSG mice may represent an important, new model for preclinical immunotherapy research.-Wang, M., Yao, L.-C., Cheng, M., Cai, D., Martinek, J., Pan, C.-X., Shi, W., Ma, A.-H., De Vere White, R. W., Airhart, S., Liu, E. T., Banchereau, J., Brehm, M. A., Greiner, D. L., Shultz, L. D., Palucka, K., Keck, J. G. Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy.
Insights
Humanized mice with human immune systems enable cancer immunotherapy research. These humanized mice showed pembrolizumab effectively inhibited tumor growth, dependent on human T cells.
Area of Science:
- Immunology
- Oncology
- Preclinical Research
Background:
- Developing in vivo models for human tumor and immune system interactions is crucial for advancing cancer immunotherapy research.
- Nonobese diabetic (NOD).Cg-PrkdcscidIL2rgtm1Wjl/Sz (NSG) mice transplanted with human CD34+ hematopoietic progenitor and stem cells develop human immune systems, creating humanized NSG (HuNSG) mice.
Purpose of the Study:
- To establish and validate a humanized mouse model for preclinical investigation of cancer immunotherapy efficacy and mechanisms.
- To assess the efficacy of PD-1 targeted therapy (pembrolizumab) in humanized mice bearing human tumor xenografts.
Main Methods:
- Humanized NSG (HuNSG) mice were engrafted with patient-derived xenografts (PDX) or cell line-derived xenografts (CDX) of non-small cell lung cancer, sarcoma, bladder cancer, and triple-negative breast cancer.
- Tumor growth was monitored in HuNSG mice and compared to non-humanized NSG mice after treatment with pembrolizumab.
- The role of human CD8+ T cells in tumor growth inhibition was evaluated using antibody-mediated depletion.
Main Results:
- HuNSG mice engrafted with human tumors exhibited similar tumor growth kinetics compared to non-humanized NSG mice.
- Pembrolizumab treatment significantly inhibited tumor growth in both CDX and PDX models in HuNSG mice, but not in NSG mice.
- Tumor growth inhibition by pembrolizumab was dependent on the presence of human CD8+ T cells.
Conclusions:
- Tumor-bearing HuNSG mice represent a valuable new preclinical model for studying cancer immunotherapy.
- This model facilitates the investigation of mechanisms underlying PD-1 targeted therapy efficacy.
- The findings support the utility of humanized mice for advancing the development of novel cancer immunotherapies.
