Oncolytic effect of Newcastle disease virus F48E9 strain on CT26 murine colon cancer
ZHONG Jian-ping1, LI Rui2, WANG Guo-song1, HONG Jun-ping1, FU Rao1, CHEN Yi-xin1, 2
1. National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University, Xiamen 361102, China; 2. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
Abstract:To evaluate the potential of Newcastle disease virulent strain F48E9 for oncolytic treatment and make a foundation of genetic modification for Newcastle disease virus F48E9 strain, the inhibitory effect of F48E9 strain on CT26 colon cancer cells was tested by CCk-8 kit in vitro and oncolytic effect of F48E9 strain on CT26 tumor-bearing mice in vivo was evaluated by intratumoral injection of F48E9 virus, the side effects of F48E9 strain on 6-week BALB/c mice was also evaluated by Intravenous injection of 2×107 pfu virus. The results showed that F48E9 at a MOI of 0.1 showed an obvious inhibition on the growth of CT26 cells. With the increase of MOI, its inhibitory effect on cell growth was significantly enhanced; the growth of CT26 murine tumor subcutaneously transplanted in BALB/c mice was significantly inhibited by 0.1 mL F48E9 strain at 2×107 pfu/mL. The average survival time of the virus-treated group was 38.4 d, and PBS-treated group was 15.2 d. Immunohistochemical experiment showed that F48E9 significantly inhibited the proliferation of CT26 cells of transplanted tumor in mice; safety evaluation of F48E9 strain by tail vein injection in normal BALB/c mice showed that the strain had no obvious side effects. The results showed that Newcastle disease virus F48E9 strain had a good therapeutic effect on CT26 colorectal cancer in vitro and in vivo and was safety on BALB/c mice. Newcastle disease virulent strain F48E9 has a good oncolytic potential for CT26 mouse colorectal cancer, and can be used as a candidate virus strain to establish a safer and more effective oncolytic virus strain through subsequent reverse genetic modification, for tumor research and treatment.
[1] 张忠涛, 蔡军. 结肠癌多学科综合治疗协作组诊疗模式专家共识[J]. 中国实用外科杂志, 2017, 1(37):44-45. DOI:10.19538/j.cjps.issn1005-2208.2017.01.15 [2] 吴琳. 结肠癌根治术后肿瘤转移复发的特点和影响预后的因素[J]. 中外医学研究, 2015, 14:127-129. DOI:10.14033/j.cnki.cfmr.2015.14.065 [3] Couzin FJ.Cancer immunotherapy[J]. Science, 2013, 342(6165):1432-1433. DOI:10.1126/Science.342.6165.1432 [4] Russell SJ, Peng KW, Bell JC.Oncolytic virotherapy[J]. Nat Biotechnol, 2012, 30(7):658-670. DOI:10.1038/nbt.2287 [5] Fountzilas C, Patel S, Mahalingam D, et al.Review:oncolytic virotherapy, updates and future directions[J]. Oncotarget, 2017, 8(60):102617-102639. DOI:10.18632/oncotarget.18309 [6] Freeman AI, Zakay RZ, Gomori JM, et al.Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme[J]. Mol Ther, 2006, 13(1):221-228. DOI:10.1016/j.Ymthe.2005.08.016 [7] Zemp FJ, Corredor JC, Lun X, et al.Oncolytic viruses as experimental treatments for malignant gliomas: using a scourge to treat a devil[J]. Cytokine Growth Factor Rev, 2010, 21(2) : 103-117. DOI:10.1016/j.Cytogfr.2010.04.001 [8] Coffin R.Interview with Robert Coffin, inventor of T-VEC: the first oncolytic immuno-therapy approved for the treatment of cancer[J]. Immunotherapy, 2016, 8(2): 103-106. DOI: 10.2217/imt.15.116 [9] Mustaffa BA, Ibrahim AL, Khim TS.A case of human infection with newcastle disease virus[J]. Southeast Asian J Trop Med Public Health, 1976, 7(4): 622-624. [10] Buijs PR, Van AG, Van NS, et al.Intravenously injected newcastle disease virus in non-human primates is safe to use for oncolytic virotherapy[J]. Cancer Gene Ther, 2014, 21(11): 463-471. DOI: 10.1038/cgt.2014.51 [11] Pecora AL, Rizvi N, Cohen GI, et al.Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers[J]. J Clin Oncol, 2002, 20(9): 2251-2266. DOI: 10.1200/JCO.2002.08.042 [12] Laurie SA, Bell JC, Atkins HL, et al.A phase 1 clinical study of intravenous administration of PV701, an oncolytic virus, using two-step desensitization[J]. Clin Cancer Res, 2006, 12(8):2555-2562. DOI: 10.1158/1078-0432.CCR-05-2038 [13] Sinkovics JG, Horvath JC.Newcastle disease virus :brief history of its oncolytic strains[J]. J Clin Virol, 2000, 16(1):1-15. DOI: 10.1016/S1386-6532(99)00072-4 [14] 胡立华, 陈鹏, 张沛怡, 等. 新城疫病毒对人类大肠癌细胞的杀伤作用研究[J]. 牡丹江医学院学报, 2010, 31(5):11-13. DOI: 10.3969/j.issn.1001-7550.2010.05.005 [15] 梅双双, 杨润德. 鸡新城疫病毒强毒株的分离及生物学特性鉴定[J]. 中国预防兽医学报, 2002, 24(5):368-371. DOI: 10.3969/j.issn.1008-0589.2002.05.013 [16] 王明睿, 钟建平, 李睿, 等. 新城疫病毒核蛋白单克隆抗体的制备及双抗体夹心ELISA的初步建立[J].中国人兽共患病学报, 2017, 33(6):481-485. DOI: 10.3969/j.issn.1002-2694.2017.06.002 [17] Vigil A, Park MS, Martinez O, et al.Use of reverse genetics to enhance the oncolytic properties of newcastle disease virus[J]. Cancer Res, 2007, 67(17):8285-8292. DOI: 10.1158/0008-5472.CAN-07-1025 [18] Kanthiya K, Khunnarong J, Tangjitgamol S, et al.Expression of the p16 and Ki67 in cervical squamous intraepithelial lesions and cancer[J]. Asian Pac J Cancer Prev, 2016, 17(7):3201-3206. DOI: 10.14456/apjcp.2016.76 [19] Zamarin D, Holmgaard RB, Subudhi SK, et al.Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy[J]. Sci Transl Med, 2014, 6(226):226-232. DOI: 10.1126/scitranslmed.3008095 [20] Patricia K, Laetitia F, Christine T, et al. Vectorization in an oncolytic vaccinia virus of an antibody, a fab and a scFv against programmed cell death-1 (PD-1) allows their intratumoral delivery and an improved tumor-growth inhibition[J]. Oncoimmunology, 2016, 5(10): e1220467.1-e1220467.14. DOI: 10.1080/2162402X.2016.1220467 [21] Ruotsalainen JJ, Kaikkonen MU, Niittykoski M, et al.Clonal variation in interferon response determines the outcome of oncolytic virotherapy in mouse CT26 colon carcinoma model[J]. Gene Ther, 2014, 22(1):65-75. DOI: 10.1038/gt.2014.83 [22] Scholzen T, Gerdes J.The ki-67 protein: from the known and the unknown[J]. J Cell Physiol, 2000, 182(3): 311-322. DOI: 10.1002/(SICI)1097-4652(200003) [23] Vigil A, Martinez O, Chua MA, et al.Recombinant newcastle disease virus as a vaccine vector for cancer therapy[J]. Mol Ther, 2008, 16(11): 1883-1890. DOI: 10.1038/mt.2008.181 [24] Hong S, Wang K, Xie R, et al.NDV-D90 suppresses growth of gastric cancer and cancer related vascularization[J]. Oncotarget, 2017, 8(21):34516-34524. DOI: 10.18632/oncotarget. 16563