A Tumor-targeting Adenovirus with High Gene-transduction Efficiency for Primary Pancreatic Cancer and Ascites Cells

被引：8

作者：

Nagasato, Masaki ^{[1
,4
]}

Rin, Yosei ^{[1
,4
]}

Yamamoto, Yuki ^{[1
,4
]}

Henmi, Marina ^{[1
,4
]}

Hiraoka, Nobuyoshi ^{[2
]}

Chiwaki, Fumiko ^{[3
]}

Matsusaki, Keisuke ^{[5
]}

Tagawa, Masatoshi ^{[6
]}

Sasaki, Hiroki ^{[3
]}

Aoki, Kazunori ^{[1
]}

机构：

[1] Natl Canc Ctr, Res Inst, Div Mol & Cellular Med, Tokyo, Japan

[2] Natl Canc Ctr, Res Inst, Div Mol Pathol, Tokyo, Japan

[3] Natl Canc Ctr, Res Inst, Dept Translat Oncol, Tokyo, Japan

[4] Tokyo Med & Dent Univ, NCC Canc Sci, Tokyo, Japan

[5] Kanamecho Hosp, Kaname Clin 2, Tokyo, Japan

[6] Chiba Canc Ctr, Res Inst, Div Pathol & Cell Therapy, Chiba, Japan

来源：

ANTICANCER RESEARCH | 2017年 / 37卷 / 07期

关键词：

Adenovirus delivery; gene therapy; pancreatic cancer; DISPLAYING RANDOM PEPTIDES; THERAPY; ADENOCARCINOMA;

D O I：

10.21873/anticanres.11730

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Optimizing targeting strategies for vectors in order to enhance antitumor activity and secure patient safety is important for cancer gene therapy. We previously identified two pancreatic cancer-targeting ligands (PFWSGAV: PFW and SYENFSA: SYE) by screening an adenovirus library in vivo and in vitro, respectively. Materials and Methods: To examine clinical usefulness, we assessed gene-transduction efficiency using surgically-resected pancreatic cancer specimens and ascites cells. Results: For surgical specimens, vectors displaying PFW and SYE improved transduction efficiency by 4.4- and 4.3-fold, respectively. The SYE-displaying vector was >2-fold more efficient for all seven cases, whereas the PFW-displaying vector increased efficiency in two out of four cases. For ascites samples, both vectors increased gene-transduction efficiency of epithelial cell adhesion molecule (EpCAM)-positive ascites cells by >2-fold in two out of five cases. Conclusion: Both vectors enhanced adenovirus infectivity of pancreatic cancer cells and have potential for gene therapy of pancreatic cancer; therefore they should be further evaluated in clinical studies.

引用

页码：3599 / 3605

页数：7

共 18 条

[1] Malignant ascites: Past, present, and future
Adam, RA
Adam, YG
[J]. JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS, 2004, 198 (06) : 999 - 1011
[2] [Anonymous], 2017, CA-CANCER J CLIN, V67, P7, DOI [DOI 10.3322/caac.21387, DOI 10.3322/CAAC.21387]
[3] Beatty MS, 2012, ADV CANCER RES, V115, P39, DOI [10.1016/B978-0-12-398342-8.00002-1, 10.1016/B978-0-12-3983,12-8.00002-1]
[4] Recent Advances and Prospects for Multimodality Therapy in Pancreatic Cancer
Chadha, Awalpreet S.
Khoo, Allison
Aliru, Maureen L.
Arora, Harpreet K.
Gunther, Jillian R.
Krishnan, Sunil
[J]. SEMINARS IN RADIATION ONCOLOGY, 2016, 26 (04) : 320 - 337
[5] A simple and efficient method for constructing an adenoviral cDNA expression library
Hatanaka, K
Ohnami, S
Yoshida, K
Miura, Y
Aoyagi, K
Sasaki, H
Asaka, M
Terada, M
Yoshida, T
Aoki, K
[J]. MOLECULAR THERAPY, 2003, 8 (01) : 158 - 166
[6] Pancreas Adenocarcinoma: Ascites, Clinical Manifestations, and Management Implications
Hicks, Angel Mier
Chou, Joanne
Capanu, Marinela
Lowery, Maeve A.
Yu, Kenneth H.
O'Reilly, Eileen M.
[J]. CLINICAL COLORECTAL CANCER, 2016, 15 (04) : 360 - 368
[7] Direct selection of targeted adenovirus vectors by random peptide display on the fiber knob
Miura, Y.
Yoshida, K.
Nishimoto, T.
Hatanaka, K.
Ohnami, S.
Asaka, M.
Douglas, J. T.
Curiel, D. T.
Yoshida, T.
Aoki, K.
[J]. GENE THERAPY, 2007, 14 (20) : 1448 - 1460
[8] Molecular targeted therapy for pancreatic adenocarcinoma: A review of completed and ongoing late phase clinical trials
Mosquera, Catalina
Maglic, Dino
Zervos, Emmanuel E.
[J]. CANCER GENETICS, 2016, 209 (12) : 567 - 581
[9] Oncolytic virus therapy for pancreatic cancer using the adenovirus library displaying random peptides on the fiber knob
Nishimoto, T.
Yoshida, K.
Miura, Y.
Kobayashi, A.
Hara, H.
Ohnami, S.
Kurisu, K.
Yoshida, T.
Aoki, K.
[J]. GENE THERAPY, 2009, 16 (05) : 669 - 680
[10] Development of Peritoneal Tumor-Targeting Vector by In Vivo Screening with a Random Peptide-Displaying Adenovirus Library
Nishimoto, Takeshi
Yamamoto, Yuki
Yoshida, Kimiko
Goto, Naoko
Ohnami, Shumpei
Aoki, Kazunori
[J]. PLOS ONE, 2012, 7 (09):

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