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Updated: Dec 10, 2025
Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes
Published on: November 11, 2016
IL2RG-deficient minipigs generated via CRISPR/Cas9 technology support the growth of human melanoma-derived tumours
Jilong Ren1,2,3, Dawei Yu1,2, Rui Fu1,2
1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Objectives:
Immunodeficient mice injected with human cancer cell lines have been used for human oncology studies and anti-cancer drug trials for several decades. However, rodents are not ideal species for modelling human cancer because rodents are physiologically dissimilar to humans. Therefore, anti-tumour drugs tested effective in rodents have a failure rate of 90% or higher in phase III clinical trials. Pigs are similar to humans in size, anatomy, physiology and drug metabolism rate, rendering them a desirable pre-clinical animal model for assessing anti-cancer drugs. However, xenogeneic immune rejection is a major barrier to the use of pigs as hosts for human tumours. Interleukin (IL)-2 receptor γ (IL2RG), a common signalling subunit for multiple immune cytokines including IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, is required for proper lymphoid development.
Materials And Methods:
IL2RG-/Y pigs were generated by CRISPR/Cas9 technology, and examined for immunodeficiency and ability to support human oncogenesis.
Results:
Compared to age-matched wild-type pigs, IL2RG-/Y pigs exhibited a severely impaired immune system as shown by lymphopenia, lymphoid organ atrophy, poor immunoglobulin function, and T- and NK-cell deficiency. Human melanoma Mel888 cells generated tumours in IL2RG-/Y pigs but not in wild-type littermates. The human tumours grew faster in IL2RG-/Y pigs than in nude mice.
Conclusions:
Our results indicate that these pigs are promising hosts for modelling human cancer in vivo, which may aid in the discovery and development of anti-cancer drugs.
Insights
Genetically engineered pigs lacking the Interleukin (IL)-2 receptor gamma chain (IL2RG) show severe immunodeficiency, enabling them to support human tumor growth. These pigs represent a promising new model for anti-cancer drug development.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Rodent models are limited for human cancer studies due to physiological differences, leading to high anti-cancer drug failure rates.
- Pigs offer physiological similarities to humans, making them ideal for pre-clinical drug assessment, but immune rejection hinders xenograft use.
- Interleukin (IL)-2 receptor gamma (IL2RG) is crucial for lymphoid development and immune function.
Purpose of the Study:
- To develop an immunodeficient pig model for human cancer xenografts.
- To assess the potential of pigs as a pre-clinical model for anti-cancer drug development.
Main Methods:
- Generated IL2RG knockout pigs using CRISPR/Cas9 gene-editing technology.
- Evaluated the immune status of IL2RG knockout pigs, including lymphopenia and immune cell deficiencies.
- Inoculated IL2RG knockout pigs with human melanoma cells to assess tumor development and growth.
Main Results:
- IL2RG knockout pigs displayed severe lymphopenia, lymphoid organ atrophy, impaired immunoglobulin function, and deficiencies in T-cells and NK-cells.
- Human melanoma Mel888 cells successfully formed tumors in IL2RG knockout pigs, unlike in wild-type littermates.
- Tumor growth in IL2RG knockout pigs was more rapid than in conventional nude mice.
Conclusions:
- IL2RG knockout pigs serve as a viable host for human cancer xenografts.
- This pig model shows potential for advancing anti-cancer drug discovery and development.
