Open AccessStrong antitumor efficacy of a pancreatic tumor‐targeting oncolytic adenovirus for neuroendocrine tumors
Author(s) -
Yamamoto Yuki,
Nagasato Masaki,
Rin Yosei,
Henmi Marina,
Ino Yoshinori,
Yachida Shinichi,
Ohki Rieko,
Hiraoka Nobuyoshi,
Tagawa Masatoshi,
Aoki Kazunori
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1185
Subject(s) - oncolytic virus , oncolytic adenovirus , pancreatic cancer , cancer research , biology , cancer cell , adenoviridae , pancreas , stromal cell , cell culture , cancer , genetic enhancement , gene , endocrinology , biochemistry , genetics , tumor cells
Although oncolytic adenoviruses are promising cancer therapy agents, for effective oncolytic activity, viruses need to specifically infect and effectively replicate in cancer cells but not in normal cells. We have previously identified a pancreatic cancer‐targeting ligand, SYENFSA ( SYE ), by screening an adenovirus library displaying random peptides against human pancreatic cancer cells and reported that a survivin promoter‐regulated adenovirus, displaying the SYE ligand (AdSur‐ SYE ), provided effective oncolysis of pancreatic ductal adenocarcinoma ( PDAC ) in a preclinical study. As we examined the infectivity of AdSur‐ SYE in human surgical specimens of various pancreatic tumors, we unexpectedly found that AdSur‐ SYE showed high gene transduction efficiency for pancreatic neuroendocrine tumors ( PNET s) as well as for PDAC , 9.1‐ and 6.2‐fold, respectively, compared to that of the nontargeting virus (AdSur). The infectivity of both vectors was almost the same in other cancers and organs such as the pancreas. Immunostaining indicated that the cells infected with AdSur‐ SYE were PNET cells but not stromal cells. AdSur‐ SYE showed a significantly higher oncolytic potency than that of AdSur in human PNET cell lines, and intratumoral infection with AdSur‐ SYE completely diminished subcutaneous tumors in a murine model, in which AdSur‐ SYE effectively proliferated and spread. AdSur‐ SYE exerted a stronger oncolytic effect in primary PNET cells cocultured with mouse embryonic fibroblasts than AdSur did. Thus, AdSur‐ SYE shows promise as a next‐generation therapy for PNET .