A folate receptor-targeted lipoplex delivering interleukin-15 gene for colon cancer immunotherapy

// Xiao Liang 1 , Min Luo 1 , Xia-Wei Wei 1 , Cui-Cui Ma 1 , Yu-Han Yang 1 , Bin Shao 1 , Yan-Tong Liu 1 , Ting Liu 1 , Jun Ren 1 , Li Liu 1 , Zhi-Yao He 1 , Yu-Quan Wei 1 1 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China Correspondence to: Zhi-Yao He, email: heyaode@163.com Yu-Quan Wei, email: yqwei@scu.edu.cn Keywords: interleukin-15, folate receptor α, colon cancer, immunotherapy, gene therapy Received: January 23, 2016     Accepted: June 16, 2016     Published: July 11, 2016 ABSTRACT Interleukin-15 has been implicated as a promising cytokine for cancer immunotherapy, while folate receptor α (FRα) has been shown to be a potentially useful target for colon cancer therapy. Herein, we developed F-PLP/pIL15, a FRα-targeted lipoplex loading recombinant interleukin-15 plasmid (pIL15) and studied its antitumor effects in vivo using a CT26 colon cancer mouse model. Compared with control (normal saline) treatment, F-PLP/pIL15 significantly suppressed tumor growth in regard to tumor weight ( P < 0.001) and reduced tumor nodule formation ( P < 0.001). Moreover, when compared to other lipoplex-treated mice, F-PLP/pIL15-treated mice showed higher levels of IL15 secreted in the serum ( P < 0.001) and ascites ( P < 0.01). These results suggested that the targeted delivery of IL15 gene might be associated with its in vivo antitumor effects, which include inducing tumor cell apoptosis, inhibiting tumor proliferation and promoting the activation of immune cells such as T cells and natural killer cells. Furthermore, hematoxylin and eosin staining of vital organs following F-PLP/pIL15 treatment showed no detectable toxicity, thus indicating that intraperitoneal administration may be a viable route of delivery. Overall, these results suggest that F-PLP/pIL15 may serve as a potential targeting preparation for colon cancer therapy.