title: Trastuzumab-Based Photoimmunotherapy Integrated with Viral HER2 Transduction Inhibits Peritoneally Disseminated HER2-Negative Cancer.
abstract: Peritoneal dissemination is the most frequent metastasis in gastric cancer and is associated with poor prognosis. The lack of particular target antigens in gastric cancer other than HER2 has hampered the development of treatments for peritoneal dissemination of gastric cancer. We hypothesized that HER2-extracellular domain (HER2-ECD) gene transduction combined with trastuzumab-based photoimmunotherapy (PIT) might provide excellent and selective antitumor effects for peritoneal dissemination of gastric cancer. In vitro, adenovirus/HER2-ECD (Ad/HER2-ECD) efficiently transduced HER2-ECD into HER2-negative gastric cancer cells. Trastuzumab-IR700 (Tra-IR700)-mediated PIT induced selective cell death of HER2-ECD-transduced tumor cells. Ad/HER2-ECD also induced homogenous expression of HER2 in heterogeneous gastric cancer cells, resulting in uniform sensitivity of the cells to Tra-IR700-mediated PIT. Anti-HER2 PIT integrated with adenoviral HER2-ECD gene transfer was applied in mice bearing peritoneal dissemination of HER2-negative gastric cancer. Intraperitoneal administration of Ad/HER2-ECD and Tra-IR700 with PIT inhibited peritoneal metastasis and prolonged the survival of mice bearing MKN45. Furthermore, minimal side effects allowed the integrated therapy to be used repeatedly, providing better control of peritoneal dissemination. In conclusion, the novel therapy of molecular-targeted PIT integrated with gene transfer technology is a promising approach for the treatment of peritoneal dissemination in gastric cancer.
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Ishida
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. skagawa@md.okayama-u.ac.jp.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kagawa
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shimoyama
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Takehara
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Noma
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tanabe
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shirakawa
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tazawa
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D008163:Luminescent Measurements; D051379:Mice; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000556:secondary* / Q000628:therapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D010789:Phototherapy; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic; D000068878:Trastuzumab / Q000494:pharmacology*; D014780:Viruses / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
references.citation: Gastric Cancer. 2013 Jan;16(1):1-27
references.pmid: 22729699
references.citation: J Natl Cancer Inst. 1998 Jun 17;90(12):889-905
references.pmid: 9637138
references.citation: Gut. 2004 Apr;53(4):554-60
references.pmid: 15016751
references.citation: Cancer Immunol Immunother. 2012 Nov;61(11):1905-16
references.pmid: 22465967
references.citation: Cancer Res. 2004 Sep 1;64(17):6259-65
references.pmid: 15342413
references.citation: Photochem Photobiol. 1992 Jan;55(1):145-57
references.pmid: 1603846
references.citation: Cancer. 2013 Sep 15;119(18):3354-8
references.pmid: 23798046
references.citation: PLoS One. 2014 Nov 17;9(11):e113276
references.pmid: 25401794
references.citation: J Gastrointest Oncol. 2015 Feb;6(1):60-74
references.pmid: 25642339
references.citation: Lancet. 2010 Aug 28;376(9742):687-97
references.pmid: 20728210
references.citation: Histopathology. 2014 Jun;64(7):1027-31
references.pmid: 24329753
references.citation: Histopathology. 2008 Jun;52(7):797-805
references.pmid: 18422971
references.citation: Surg Today. 2014 Mar;44(3):399-404
references.pmid: 23677598
references.citation: Ann Surg Oncol. 2011 Oct;18(10):2833-40
references.pmid: 21468783
references.citation: Cancer Sci. 2009 Oct;100(10):1979-85
references.pmid: 19604244
references.citation: Cell Biochem Biophys. 2012 Jan;62(1):221-8
references.pmid: 21927816
references.citation: Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):285-92
references.pmid: 14734481
references.citation: Exp Cell Res. 2000 Feb 25;255(1):47-55
references.pmid: 10666333
references.citation: Ann Oncol. 2013 Mar;24(3):725-33
references.pmid: 23139264
references.citation: Gastric Cancer. 2011 Oct;14(4):301-16
references.pmid: 21894577
references.citation: Br J Surg. 2000 Feb;87(2):236-42
references.pmid: 10671934
references.citation: Nat Med. 2011 Apr;17(4):416-8
references.pmid: 21475230
references.citation: Lancet Oncol. 2011 Jan;12(1):16-7
references.pmid: 21249723
references.citation: Ann Oncol. 2013 Sep;24(9):2360-4
references.pmid: 23788757
references.citation: Nat Med. 2011 Nov 06;17(12):1685-91
references.pmid: 22057348
references.citation: Int J Cancer. 2014 Dec 1;135(11):2697-710
references.pmid: 24740257
references.citation: Eur J Cancer. 2004 Sep;40(14):2135-42
references.pmid: 15341989
references.citation: Mitochondrion. 2004 Sep;4(5-6):559-67
references.pmid: 16120414
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14514-7
references.pmid: 19706537
references.citation: Eur J Surg Oncol. 2013 Dec;39(12):1309-16
references.pmid: 24183797
references.citation: World J Surg. 2014 Feb;38(2):426-30
references.pmid: 24114368
references.citation: Ger Med Sci. 2008 Jul 21;6:Doc08
references.pmid: 19675735
references.citation: J Clin Oncol. 2010 Jan 1;28(1):92-8
references.pmid: 19933921
references.citation: J Clin Laser Med Surg. 2003 Apr;21(2):67-74
references.pmid: 12737646
references.citation: Nat Med. 2011 Apr;17(4):461-9
references.pmid: 21399647
references.citation: Breast Cancer Res Treat. 2015 Feb;149(3):597-605
references.pmid: 25616354
references.citation: J Gastrointestin Liver Dis. 2009 Jun;18(2):189-95
references.pmid: 19565050
references.citation: Target Oncol. 2012 Dec;7(4):213-6
references.pmid: 22752927
references.citation: Mol Cancer Ther. 2015 Jan;14(1):141-50
references.pmid: 25416790
references.citation: Ann Oncol. 2013 Jul;24(7):1754-1761
references.pmid: 23524864
references.citation: Eur J Cancer. 2013 Apr;49(6):1448-57
references.pmid: 23146959
references.citation: Jpn J Clin Oncol. 2013 Mar;43(3):324-7
references.pmid: 23275644
references.citation: Eur J Surg Oncol. 2007 Oct;33(8):988-92
references.pmid: 17344017
references.citation: Mod Pathol. 2012 May;25(5):637-50
references.pmid: 22222640
references.citation: CA Cancer J Clin. 2015 Mar;65(2):87-108
references.pmid: 25651787
references.citation: Nat Genet. 2014 Jun;46(6):573-82
references.pmid: 24816253
references.citation: Cancer Cell. 2004 Aug;6(2):117-27
references.pmid: 15324695
references.citation: Anticancer Res. 2012 Sep;32(9):4071-5
references.pmid: 22993363