<i>Plasmodium</i> parasite as an effective hepatocellular carcinoma antigen glypican-3 delivery vector

Abstract

// Quan Liu 1 , Yijun Yang 1 , Xuefang Tan 1 , Zhu Tao 1 , Dickson Adah 1 , Songlin Yu 1 , Junnan Lu 1 , Siting Zhao 1 , Limei Qin 1 , Li Qin 1 , Xiaoping Chen 1 1 Laboratory of Pathogen Biology, State Key Laboratory of Respiratory Diseases, Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, Guangzhou, China Correspondence to: Xiaoping Chen, email: chen_xiaoping@gibh.ac.cn Li Qin, email: qin_li@gibh.ac.cn Limei Qin, email: qin_limei@gibh.ac.cn Keywords: GPC3, vector, plasmodium parasite, hepatocellular carcinoma, immunotherapy Received: December 08, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: February 15, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: March 01, 2017 ABSTRACT We have previously demonstrated that malaria parasite infection has an anti-tumor effect in a mouse model. This research aimed to investigate the possibility of using Plasmodium parasite as a novel vaccine vector for hepatocellular carcinoma (HCC) immunotherapy. We constructed a Plasmodium yoelii 17XNL strain (P.y) expressing murine glypican-3 (GPC3) protein ( P . y -GPC3), and examined its therapeutic potency in a murine Hepa1-6-induced hepatoma model that highly expressed GPC3 protein. The prerequisites for invoking a CD8+ T cell response were assessed after P . y -based immunization, which included obviously increased concentrations of T helper cell type 1 (Th1)-associated cytokines, such as IL-2, IFN-&gamma; and TNF-&alpha;, in serum and preferential expansion of the CD8&alpha;+ dendritic cell (DC) subset with higher expression of CD80 and CD86 molecules. Compared with uninfected and wild-type P . y -infected mice, a significant GPC3-specific cytotoxic T lymphocyte (CTL) response was detected in P . y - GPC3 vaccinated mice. Furthermore, P . y - GPC3 -based vaccination dramatically inhibited Hepa1-6-induced tumor growth in the implanted HCC and prolonged the survival of tumor-bearing mice. We concluded that a Plasmodium -based vector is highly efficient in inducing tumor antigen-specific T cell-mediated immunity and protection against tumor cells. More broadly, this strategy supported our hypothesis that Plasmodium parasites, as novel therapeutic antigen vectors, may be applicable to tumor immunotherapy for patients with HCC.