title: Combined therapy with CTL cells and oncolytic adenovirus expressing IL-15-induced enhanced antitumor activity.
abstract: Addition of immunoregulation factor to an oncolytic adenovirus being constructed is a developmental step in tumor gene therapy; however, cytokine IL-15 has not been frequently used as a potential cancer therapy agent. Here, we constructed an E2F-1 promoter oncolytic adenovirus based on type 5 adenovirus, which induces viral replication and proliferation in targeted tumor cells. We inserted the IL-15 gene into the E3 region of the model and found that human IL-15 expressing oncolytic adenovirus (Ad-E2F/IL15) shows a more intense antitumor effect than simple oncolytic viruses (Ad-E2F) do. Precisely because IL-15 can activate natural killer (NK) cells, CD8(+)T cells, and other immune cells, in antitumor therapy, Ad-E2F/IL15 was used in combination with cytotoxic T lymphocytes (CTL) to create a virus that can induce IL-15 gene expression while lysing tumors and stimulating the activity and function of adoptive immune cells. The therapeutic effect of this therapy is clearly stronger than that of a single application of oncolytic viruses or CTL, and hence, it could be a potential new tumor therapy.
authors: General Surgery Department, Chinese PLA General Hospital, 28 Fuxing Road, Haidian, Beijing, 100853, People's Republic of China.
authors: Yang
authors: Y
authors: Yan
authors: Songyan
authors: S
authors: Li
authors: Tingting
authors: T
authors: Jia
authors: Xiaohui
authors: X
authors: Du
authors: Yingxin
authors: Y
authors: Xu
authors: Yunshan
authors: Y
authors: Zhao
authors: Li
authors: L
authors: Li
authors: Kai
authors: K
authors: Liang
authors: Wentao
authors: W
authors: Liang
authors: Huiwei
authors: H
authors: Sun
authors: Rong
authors: R
authors: Li
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D005786:Gene Expression Regulation / Q000276:immunology; D005822:Genetic Vectors; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D019409:Interleukin-15
references: Curr Opin Immunol. 2014 Apr;27:46-52
references: 24534448
references: Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16168-73
references: 12427970
references: Curr Cancer Drug Targets. 2007 Mar;7(2):133-9
references: 17346104
references: Oncol Rep. 2012 Nov;28(5):1743-9
references: 22948809
references: Cytokine Growth Factor Rev. 2010 Apr-Jun;21(2-3):153-9
references: 20395162
references: Mol Ther. 2011 Aug;19(8):1558-68
references: 21468000
references: Cancer Res. 2002 Jul 1;62(13):3743-50
references: 12097284
references: Oncol Lett. 2013 Feb;5(2):489-494
references: 23420461
references: Mol Ther. 2010 Nov;18(11):1972-82
references: 20700112
references: Nat Rev Clin Oncol. 2011 Aug 02;8(10):577-85
references: 21808266
references: Exp Ther Med. 2012 Aug;4(2):221-225
references: 23139711
references: Cancer Res. 2010 Feb 1;70(3):1072-81
references: 20086176
references: Eur J Immunol. 2007 Jun;37(6):1678-90
references: 17492620
references: Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11445-50
references: 11016962
references: J Clin Invest. 2007 Jun;117(6):1466-76
references: 17549249
references: Adv Drug Deliv Rev. 2012 Jun 1;64(8):720-9
references: 22212901
references: Nat Biotechnol. 2012 Jul 10;30(7):658-70
references: 22781695
references: Curr Gene Ther. 2013 Feb;13(1):15-30
references: 23157547
references: Hepatobiliary Pancreat Dis Int. 2009 Jun;8(3):282-7
references: 19502169
references: Curr Gene Ther. 2009 Oct;9(5):422-7
references: 19860656
references: Curr Pharm Biotechnol. 2012 Jul;13(9):1809-16
references: 21740362
references: J Leukoc Biol. 2010 Sep;88(3):529-36
references: 20538758
references: Cancer Gene Ther. 2012 Apr;19(4):238-46
references: 22158521
references: Nat Rev Cancer. 2008 Apr;8(4):299-308
references: 18354418
references: J Immunol. 2002 Nov 1;169(9):4928-35
references: 12391205
references: J Virol. 2009 Jun;83(11):5933-8
references: 19279088
references: Tumour Biol. 2014 Feb;35(2):1113-22
references: 24037896
references: Int J Cancer. 2002 Jun 1;99(4):573-8
references: 11992548
references: J Exp Med. 2000 Mar 6;191(5):771-80
references: 10704459
references: Clin Cancer Res. 2009 Feb 15;15(4):1145-54
references: 19228720
references: Clin Cancer Res. 2006 Jan 1;12(1):305-13
references: 16397056
references: Hepatology. 2009 Jan;49(1):124-32
references: 18980227
references: J Pathol. 2004 Jul;203(3):744-53
references: 15221933
references: Cancer Gene Ther. 2009 Jun;16(6):473-88
references: 19197323
references: Acta Pharmacol Sin. 2009 Apr;30(4):467-77
references: 19270721
references: Cytokine Growth Factor Rev. 2011 Apr;22(2):99-108
references: 21531164
references: Immunity. 1998 Nov;9(5):669-76
references: 9846488
references: J Gastroenterol. 2005 Jan;40(1):31-42
references: 15692787
references: N Engl J Med. 2010 Jul 29;363(5):411-22
references: 20818862
references: Cancer Gene Ther. 2007 Nov;14(11):918-26
references: 17693992
references: PLoS One. 2012;7(9):e44802
references: 23028626
references: Cancer Res. 2001 Jan 15;61(2):517-25
references: 11212244
references: Cancer Gene Ther. 2013 Feb;20(2):70-6
references: 23306610
references: Expert Rev Anticancer Ther. 2008 Oct;8(10):1581-8
references: 18925850