Theranostics 2018; 8(13):3490-3503. doi:10.7150/thno.24157

Research Paper

Powerful anti-colon cancer effect of modified nanoparticle-mediated IL-15 immunogene therapy through activation of the host immune system

Xiaoxiao Liu1,2,3,*, Yanyan Li4,*, Xiaodong Sun1,*, Yagmur Muftuoglu5, Bilan Wang3, Ting Yu1, Yuzhu Hu1, Lu Ma1, Mingli Xiang1, Gang Guo1, Chao You1, Xiang Gao1,✉, Yuquan Wei1

1. Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University/Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
2. Department of Radiation Oncology, Cancer Center, Affiliated Hospital of Xuzhou Medical University; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, 221000, China.
3. Department of Pharmacy, West China Second University Hospital of Sichuan University, Chengdu, 610041, China.
4. Department of radiation oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
5. Stanford University School of Medicine, Stanford, CA 94305, USA
*These authors are considered equal first authors.

Abstract

Rationale: Colorectal cancer (CRC) is the third most commonly diagnosed cancer around the world. Over the past several years, immunotherapy has demonstrated considerable clinical benefit in CRC therapy, and the number of immunologic therapies for cancer treatment continues to climb each year. Interleukin-15 (IL15), a potent pro-inflammatory cytokine, has emerged as a candidate immunomodulator for the treatment of CRC.

Methods: In this study, we developed a novel gene delivery system with a self-assembly method using DOTAP and MPEG-PLA (DMA) to carry pIL15, denoted as DMA-pIL15 which was used to treat tumor-bearing mice.

Results: Supernatant from lymphocytes treated with supernatant derived from CT26 cells transfected with DMA-pIL15 inhibited the growth of CT26 cells and induced cell apoptosis in vitro. Treatment of tumor-bearing mice with DMA-pIL15 complex significantly inhibited tumor growth in both subcutaneous and peritoneal models in vivo by inhibiting angiogenesis, promoting apoptosis, and reducing proliferation through activation of the host immune system.

Conclusion: The IL-15 plasmid and DMA complex showed promise for treating CRC clinically as an experimental new drug.

Keywords: colorectal cancer, immunotherapy, interleukin-15, MPEG-PLA, DOTAP

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How to cite this article:
Liu X, Li Y, Sun X, Muftuoglu Y, Wang B, Yu T, Hu Y, Ma L, Xiang M, Guo G, You C, Gao X, Wei Y. Powerful anti-colon cancer effect of modified nanoparticle-mediated IL-15 immunogene therapy through activation of the host immune system. Theranostics 2018; 8(13):3490-3503. doi:10.7150/thno.24157. Available from http://www.thno.org/v08p3490.htm