Open AccessIL2RG ‐deficient minipigs generated via CRISPR/Cas9 technology support the growth of human melanoma‐derived tumours
Author(s) -
Ren Jilong,
Yu Dawei,
Fu Rui,
An Peipei,
Sun Renren,
Wang Zhengzhu,
Guo Runfa,
Li Haoyun,
Zhang Ying,
Li Ziyi,
Yang YongGuang,
Li Wei,
Hai Tang,
Hu Zheng
Publication year - 2020
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12863
Subject(s) - immune system , cancer , melanoma , biology , medicine , immunology , severe combined immunodeficiency , cancer research , pharmacology , in vivo , microbiology and biotechnology
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.