Antitumor activity of recombinant oncolytic vaccinia virus with human IL2

被引:5
作者
Liu, Liqiong [2 ]
Li, Huiqun [2 ]
Xu, Qinggang [1 ]
Wu, Yan [1 ]
Chen, Dongfeng [1 ]
Yu, Feng [1 ]
机构
[1] Jiangsu Univ, Sch Life Sci, 301 Xuefu Rd, Zhenjiang 212013, Jiangsu, Peoples R China
[2] Huazhong Univ Sci & Technol, Dept Hematol, Union Shenzhen Hosp, Shenzhen 518052, Guangdong, Peoples R China
关键词
thymidine kinase; viral growth factor; human interleukin-2; oncolytic vaccinia; tumor; INTERLEUKIN-2; THERAPY; CANCER; IMMUNOTHERAPY; CHEMOKINES; SURVIVAL; MELANOMA; JX-594; TRIAL; CELLS;
D O I
10.1515/med-2022-0496
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The tumor microenvironment is highly immunosuppressive. The genetically modified oncolytic vaccinia virus (OVV) is a promising vector for cancer immunotherapy. The aim of the present study was to assess the antitumor effects of human interleukin-2 (hIL2)-armed OVV in vitro. The hIL2 gene was inserted into a thymidine kinase and the viral growth factor double deleted oncolytic VV (VVDD) to generate recombinant hIL2-armed OVV (rVVDD-hIL2). Viral replication capacity in A549 cells was quantified by plaque titration on CV-1 cells. Production of hIL2 in cancer cells infected by rVVDD-hIL2 was measured by enzyme-linked immunosorbent assay. Finally, 3-(4,5-dimethylthiazol-2-yl)-5-(3-arboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay was performed to assess the antitumor effects of rVVDD-hIL2. The results showed that rVVDD-hIL2 viral particles expressed increasing levels of hIL2 in human and murine cancer cell lines with growing multiplicities of infection (MOIs). The insertion of the hIL2 gene did not impair the replication capacity of VV, and the rVVDD-hIL2 virus killed cancer cells efficaciously. The lytic effects of the recombinant oncolytic virus on tumor cells increased with the growing MOIs. In conclusion, these findings suggest that hIL2-armed VVDD effectively infects and lyses tumor cells, with high expression of hIL2.
引用
收藏
页码:1084 / 1091
页数:8
相关论文
共 40 条
[1]   Revisiting IL-2: Biology and therapeutic prospects [J].
Abbas, Abul K. ;
Trotta, Eleonora ;
Simeonov, Dimitre R. ;
Marson, Alexander ;
Bluestone, Jeffrey A. .
SCIENCE IMMUNOLOGY, 2018, 3 (25)
[2]   Phase II trial of hu14.18-IL2 for patients with metastatic melanoma [J].
Albertini, Mark R. ;
Hank, Jacquelyn A. ;
Gadbaw, Brian ;
Kostlevy, Jordan ;
Haldeman, Jennifer ;
Schalch, Heidi ;
Gan, Jacek ;
Kim, KyungMann ;
Eickhoff, Jens ;
Gillies, Stephen D. ;
Sondel, Paul M. .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2012, 61 (12) :2261-2271
[3]  
Amedei A, 2013, RECENT PAT ANTI-CANC, V8, P126
[4]   The potential role of immunotherapy to treat colorectal cancer [J].
Amin, Manik ;
Lockhart, Albert Craig .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2015, 24 (03) :329-344
[5]  
Atkins MB, 2000, CANCER J SCI AM, V6, pS11
[6]   Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix [J].
Carnemolla, B ;
Borsi, L ;
Balza, E ;
Castellani, P ;
Meazza, R ;
Berndt, A ;
Ferrini, S ;
Kosmehl, H ;
Neri, D ;
Zardi, L .
BLOOD, 2002, 99 (05) :1659-1665
[7]   The proinflammatory cytokines IL-2, IL-15 and IL-21 modulate the repertoire of mature human natural killer cell receptors [J].
de Rham, Casimir ;
Ferrari-Lacraz, Sylvie ;
Jendly, Sabrina ;
Schneiter, Gregory ;
Dayer, Jean-Michel ;
Villard, Jean .
ARTHRITIS RESEARCH & THERAPY, 2007, 9 (06)
[8]   Phase 1 Study of Intravenous Oncolytic Poxvirus (vvDD) in Patients With Advanced Solid Cancers [J].
Downs-Canner, Stephanie ;
Guo, Zong Sheng ;
Ravindranathan, Roshni ;
Breitbach, Caroline J. ;
O'Malley, Mark E. ;
Jones, Heather L. ;
Moon, Anne ;
McCart, Judith Andrea ;
Shuai, Yongli ;
Zeh, Herbert J. ;
Bartlett, David L. .
MOLECULAR THERAPY, 2016, 24 (08) :1492-1501
[9]   Fueling Cancer Immunotherapy With Common Gamma Chain Cytokines [J].
Dwyer, Connor J. ;
Knochelmann, Hannah M. ;
Smith, Aubrey S. ;
Wyatt, Megan M. ;
Rivera, Guillermo O. Rangel ;
Arhontoulis, Dimitrios C. ;
Bartee, Eric ;
Li, Zihai ;
Rubinstein, Mark P. ;
Paulos, Chrystal M. .
FRONTIERS IN IMMUNOLOGY, 2019, 10
[10]   Innate and adaptive immune cells in the tumor microenvironment [J].
Gajewski, Thomas F. ;
Schreiber, Hans ;
Fu, Yang-Xin .
NATURE IMMUNOLOGY, 2013, 14 (10) :1014-1022