Efficient Colorectal Cancer Gene Therapy with IL-15 mRNA Nanoformulation
Abstract
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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A pro-inflammatory tumour microenvironment can be induced by lipid nanoparticle-mRNA formulations delivering cytokines or co-stimulatory molecules.
“Alternatively to vaccination, a pro-inflammatory tumour microenvironment can be induced by lipid nanoparticle–mRNA formulations delivering cytokines or co-stimulatory molecules33,106,161,163,214 (Table 2).”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [33]
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- Authors
- Lei, S., Zhang, X., Men, K., Gao, Y., Yang, X., Wu, S., Duan, X., Wei, Y., & Tong, R.
- Affiliations
- West China Medical Center of Sichuan University (CN)
- Sichuan University (CN)
- University of Electronic Science and Technology of China (CN)
- Corresponding author
- Men, Ke
- Tong, Rongsheng
- ORCID
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-08-10
- Volume
- 17
- Issue
- 9
- Pages
- 3378-3391
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- OpenAlex
- W3048475940
- Cited by
- 83
- References
- 45
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 18 · 2023: 16 · 2022: 16 · 2021: 5
- FWCI
- 3.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- ???Key Research and Development Program of Science and Technology Department of Sichuan Province (2020YFS0200)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- colorectal cancer, IL-15, immunogene therapy, mRNA delivery, cytokine gene therapy, lymphocyte stimulation, metastasis
- MeSH terms
- Animals, Cell Line, Chemistry, Pharmaceutical, Colonic Neoplasms, Disease Models, Animal, Female, Humans, Liposomes, Lymphocytes, Mice, Inbred BALB C, Neoplasm Metastasis, RNA, Messenger, 3T3 Cells, Interleukin-15, Mice, Nanoparticles, HEK293 Cells
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