Tumorigenicity Assessment of Human Cancer Cell Lines Xenografted on Immunodeficient Mice as Positive Controls of Tumorigenicity Testing

被引:4
|
作者
Oh, Seunghee [1 ]
Gu, Eun-Young [1 ]
Han, Ji-Seok [1 ]
Lee, Byoung-Seok [1 ]
Moon, Kyoung-Sik [1 ]
Kim, Yong-Bum [1 ]
Han, Kang-Hyun [1 ]
机构
[1] Korea Inst Toxicol, Dept Adv Toxicol Res, 141 Gajeong Ro, Daejeon 34114, South Korea
关键词
preclinical safety assessment; tumorigenicity assessment guidelines; human pluripotent stem cell therapy; gene therapy; good laboratory practice; human-derived cancer cell line; positive control; xenograft mouse model; PLURIPOTENT STEM-CELLS; SPINAL-CORD-INJURY; BLOOD;
D O I
10.1177/10915818221124573
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Recent advances in human pluripotent stem cell (hPSC)-derived cell therapies and genome editing technologies such as CRISPR/Cas9 make regenerative medicines promising for curing diseases previously thought to be incurable. However, the possibility of off-target effects during genome editing and the nature of hPSCs, which can differentiate into any cell type and infinitely proliferate, inevitably raises concerns about tumorigenicity. Tumorigenicity acts as a major obstacle to the application of hPSC-derived and gene therapy products in clinical practice. Thus, regulatory authorities demand mandatory tumorigenicity testing as a key pre-clinical safety step for the products. In the tumorigenicity testing, regulatory guidelines request to include human cancer cell line injected positive control group (PC) animals, which must form tumors. As the validity of the whole test is determined by the tumor-forming rates (typically above 90%) of PC animals, establishing the stable tumorigenic condition of PC animals is critical for successful testing. We conducted several studies to establish the proper positive control conditions, including dose, administration routes, and the selection of cell lines, in compliance with Good Laboratory Practice (GLP) regulations and/or guidelines, which are essential for pre-clinical safety tests of therapeutic materials. We expect that our findings provide insights and practical information to create a successful tumorigenicity test and its guidelines.
引用
收藏
页码:476 / 487
页数:12
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