期刊
MOLECULAR PHARMACEUTICS
卷 17, 期 9, 页码 3378-3391出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.0c00451
关键词
IVT mRNA; cancer gene therapy; IL-15; gene delivery
资金
- National Major Scientific and Technological Special Project for Significant New Drugs Development [2018ZX09733001-006-008]
- Key Research and Development Program of Science and Technology Department of Sichuan Province [2019YFS0514, 2020YFS0200]
- Postdoctoral Foundation of China [2017M612975]
Immunogene therapy is a novel method for the treatment of colorectal cancer. Cytokine IL-15 has exhibited therapeutic anticancer potential due to its immune-stimulation property. However, conventional IL-15-based cancer gene therapy studies have been performed using the plasmid DNA form, which has potential shortcomings including weak delivery efficiency and backbone effect. In this study, an IL-15 immunogene therapy study for colon cancer using in vitro transcript mRNA is described. A protamine/liposome system (CLPP) is developed to provide efficient condensation and delivery capacity for in vivo mRNA transportation. They demonstrated that the prepared CLPP system could deliver the IL-15-encoding mRNA into C26 cells with high efficacy. The secretory expressed IL-15 cytokine by the C26 cells successfully produced lymphocyte stimulation and triggered anticancer cytotoxicity upon cancer cells in vitro. Local or systemic administration of the CLPP/mIL-15 complex exhibited obvious inhibition effects on multiple C26 murine colon cancer models with inhibition rates of up to 70% in the C26 abdominal cavity metastasis tumor model, 55% in the subcutaneous model, and 69% in the pulmonary metastasis model, demonstrating high efficacy and safety. These results successfully demonstrated the high therapeutic potential of the CLPP/mIL-15 complex for colorectal cancer immunogene therapy.
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