Inhibition of colorectal cancer liver metastasis in BALB/c mice following intratumoral injection of oncolytic herpes simplex virus type 2 for the induction of specific antitumor immunity

Zhang,Wen; Wang,Feifei; Hu,Xiao; Liang,Jing; Liu,Binlei; Guan,Qi; Liu,Shangmei

doi:10.3892/ol.2018.9720

Inhibition of colorectal cancer liver metastasis in BALB/c mice following intratumoral injection of oncolytic herpes simplex virus type 2 for the induction of specific antitumor immunity

Authors:
- Wen Zhang
- Feifei Wang
- Xiao Hu
- Jing Liang
- Binlei Liu
- Qi Guan
- Shangmei Liu
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Affiliations: Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China, Department of Hematology and Oncology, The Second Clinical Medical School of Inner Mongolia University for Nationalities, Yakeshi, Inner Mongolia 022150, P.R. China
Published online on: November 16, 2018 https://doi.org/10.3892/ol.2018.9720
Pages: 815-822
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver metastasis represents the most prominent metastasis of colorectal cancer (CRC) and is the leading cause of CRC mortality, making the early prevention of this event very important. While current CRC therapies include surgery, radiotherapy and chemotherapy, no effective treatment option for CRC liver metastasis (CRLM) exists. Furthermore, the effects of currently available metastatic CRC drugs are frequently limited by their toxicity and side effects. Oncolytic herpes simplex virus type 2 (oHSV2) selectively infects tumor cells and also induces an antitumor immune response. The present study investigated the cytopathic effects of oHSV2 on CT‑26 cells in vitro and tested its inhibitory effect on CRLM. In vitro experimental data demonstrated that oHSV2 effectively inhibited the growth of CT‑26 cells. In vivo study data demonstrated that treatment with oHSV2 alone slowed the growth of subcutaneous xenograft tumors without inducing weight loss and also inhibited CRLM by increasing the numbers of cluster of differentiation (CD)4+ T, CD8+ T and natural killer cells. In summary, oHSV2 shows potential as a safe and effective therapeutic agent for inhibiting the metastasis of CT‑26 CRC cells to the liver.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Goss PE, Strasser-Weippl K, Lee-Bychkovsky BL, Fan L, Li J, Chavarri-Guerra Y, Liedke PE, Pramesh CS, Badovinac-Crnjevic T, Sheikine Y, et al: Challenges to effective cancer control in China, India and Russia. Lancet Oncol. 15:489–538. 2014. View Article : Google Scholar : PubMed/NCBI
3	Varghese C and Shin HR: Strengthening cancer control in China. Lancet Oncol. 15:484–485. 2014. View Article : Google Scholar : PubMed/NCBI
4	Adam R: Chemotherapy and surgery: New perspectives on the treatment of unresectable liver metastases. Ann Oncol. 14 Suppl 2:ii13–ii16. 2003. View Article : Google Scholar : PubMed/NCBI
5	Salah S, Ardissone F, Gonzalez M, Gervaz P, Riquet M, Watanabe K, Zabaleta J, Al-Rimawi D, Toubasi S, Massad E, et al: Pulmonary metastasectomy in colorectal cancer patients with previously resected liver metastasis: Pooled analysis. Ann Surg Oncol. 22:1844–1850. 2015. View Article : Google Scholar : PubMed/NCBI
6	Van den Eynde M and Hendlisz A: Treatment of colorectal liver metastases: A review. Rev Recent Clin Trials. 4:56–62. 2009. View Article : Google Scholar : PubMed/NCBI
7	Maffione AM, Lopci E, Bluemel C, Giammarile F, Herrmann K and Rubello D: Diagnostic accuracy and impact on management of (18)F-FDG PET and PET/CT in colorectal liver metastasis: A meta-analysis and systematic review. Eur J Nucl Med Mol Imaging. 42:152–163. 2015. View Article : Google Scholar : PubMed/NCBI
8	Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, Kemeny N, Brennan MF, Blumgart LH and D'Angelica M: Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 25:4575–4580. 2007. View Article : Google Scholar : PubMed/NCBI
9	Fong Y, Fortner J, Sun RL, Brennan MF and Blumgart LH: Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: Analysis of 1001 consecutive cases. Ann Surg. 230:309–321. 1999. View Article : Google Scholar : PubMed/NCBI
10	House MG, Kemeny NE, Gonen M, Fong Y, Allen PJ, Paty PB, DeMatteo RP, Blumgart LH, Jarnagin WR and D'Angelica MI: Comparison of adjuvant systemic chemotherapy with or without hepatic arterial infusional chemotherapy after hepatic resection for metastatic colorectal cancer. Ann Surg. 254:851–856. 2011. View Article : Google Scholar : PubMed/NCBI
11	Kobuchi S, Ito Y, Hayakawa T, Nishimura A, Shibata N, Takada K and Sakaeda T: Pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation of 5-fluorouracil for erythropenia in rats. J Pharmacol Toxicol Methods. 70:134–144. 2014. View Article : Google Scholar : PubMed/NCBI
12	Fu X, Tao L, Cai R, Prigge J and Zhang X: A mutant type 2 herpes simplex virus deleted for the protein kinase domain of the ICP10 gene is a potent oncolytic virus. Mol Ther. 13:882–890. 2006. View Article : Google Scholar : PubMed/NCBI
13	Anzivino E, Fioriti D, Mischitelli M, Bellizzi A, Barucca V, Chiarini F and Pietropaolo V: Herpes simplex virus infection in pregnancy and in neonate: Status of art of epidemiology, diagnosis, therapy and prevention. Virol J. 6:402009. View Article : Google Scholar : PubMed/NCBI
14	Zhao Q, Zhang W, Ning Z, Zhuang X, Lu H, Liang J, Li J, Zhang Y, Dong Y, Zhang Y, et al: A novel oncolytic herpes simplex virus type 2 has potent anti-tumor activity. PloS One. 9:e931032014. View Article : Google Scholar : PubMed/NCBI
15	Li H, Dutuor A, Fu X and Zhang X: Induction of strong antitumor immunity by an HSV-2-based oncolytic virus in a murine mammary tumor model. J Gene Med. 9:161–169. 2007. View Article : Google Scholar : PubMed/NCBI
16	Fu X, Tao L and Zhang X: An oncolytic virus derived from type 2 herpes simplex virus has potent therapeutic effect against metastatic ovarian cancer. Cancer Gene Ther. 14:480–487. 2007. View Article : Google Scholar : PubMed/NCBI
17	Workenhe ST, Simmons G, Pol JG, Lichty BD, Halford WP and Mossman KL: Immunogenic HSV-mediated oncolysis shapes the antitumor immune response and contributes to therapeutic efficacy. Mol Ther. 22:123–131. 2014. View Article : Google Scholar : PubMed/NCBI
18	Bollino D, Colunga A, Li B and Aurelian L: ΔPK oncolytic activity includes modulation of the tumor cell milieu. J Gen Virol. 97:496–508. 2016. View Article : Google Scholar : PubMed/NCBI
19	Colunga AG, Laing JM and Aurelian L: The HSV-2 mutant DeltaPK induces melanoma oncolysis through nonredundant death programs and associated with autophagy and pyroptosis proteins. Gene Ther. 17:315–327. 2010. View Article : Google Scholar : PubMed/NCBI
20	Yang H, Peng T, Li J, Wang Y, Zhang W, Zhang P, Peng S, Du T, Li Y, Yan Q and Liu B: Treatment of colon cancer with oncolytic herpes simplex virus in preclinical models. Gene Ther. 23:450–459. 2016. View Article : Google Scholar : PubMed/NCBI
21	Kozlowski JM, Fidler IJ, Campbell D, Xu ZL, Kaighn ME and Hart IR: Metastatic behavior of human tumor cell lines grown in the nude mouse. Cancer Res. 44:3522–3529. 1984.PubMed/NCBI
22	Yin L, Zhao C, Han J, Li Z, Zhen Y, Xiao R, Xu Z and Sun Y: Antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo. Ther Clin Risk Manag. 13:117–130. 2017. View Article : Google Scholar : PubMed/NCBI
23	Yang H, Peng T, Li J, Wang Y, Zhang W, Zhang P, Peng S, Du T, Li Y, Yan Q and Liu B: Treatment of colon cancer with oncolytic herpes simplex virus in preclinical models. Gene Ther. 23:450–459. 2016. View Article : Google Scholar : PubMed/NCBI
24	Fu X, Rivera A, Tao L and Zhang X: An HSV-2 based oncolytic virus can function as an attractant to guide migration of adoptively transferred T cells to tumor sites. Oncotarget. 6:902–914. 2015. View Article : Google Scholar : PubMed/NCBI
25	Toda M, Rabkin SD, Kojima H and Martuza RL: Herpes simplex virus as an in situ cancer vaccine for the induction of specific anti-tumor immunity. Hum Gene Ther. 10:385–393. 1999. View Article : Google Scholar : PubMed/NCBI
26	Ottolino-Perry K, Acuna SA, Angarita FA, Sellers C, Zerhouni S, Tang N and McCart JA: Oncolytic vaccinia virus synergizes with irinotecan in colorectal cancer. Mol Oncol. 9:1539–1552. 2015. View Article : Google Scholar : PubMed/NCBI
27	Esin E and Yalcin S: Maintenance strategy in metastatic colorectal cancer: A systematic review. Cancer Treat Rev. 42:82–90. 2016. View Article : Google Scholar : PubMed/NCBI
28	Russell SJ, Peng KW and Bell JC: Oncolytic virotherapy. Nat Biotechnol. 30:658–670. 2012. View Article : Google Scholar : PubMed/NCBI
29	Sze DY, Reid TR and Rose SC: Oncolytic virotherapy. J Vasc Interv Radiol. 24:1115–1122. 2013. View Article : Google Scholar : PubMed/NCBI
30	Pol J, Kroemer G and Galluzzi L: First oncolytic virus approved for melanoma immunotherapy. Oncoimmunology. 5:e11156412015. View Article : Google Scholar : PubMed/NCBI
31	Shinozaki K, Ebert O and Woo SL: Eradication of advanced hepatocellular carcinoma in rats via repeated hepatic arterial infusions of recombinant VSV. Hepatology. 41:196–203. 2005. View Article : Google Scholar : PubMed/NCBI
32	Fong Y, Kim T, Bhargava A, Schwartz L, Brown K, Brody L, Covey A, Karrasch M, Getrajdman G, Mescheder A, et al: A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer. Mol Ther. 17:389–394. 2009. View Article : Google Scholar : PubMed/NCBI
33	Toda M, Rabkin SD, Kojima H and Martuza RL: Herpes simplex virus as an in situ cancer vaccine for the induction of specific anti-tumor immunity. Hum Gene Ther. 10:385–393. 1999. View Article : Google Scholar : PubMed/NCBI
34	Shi Y, Liu CH, Roberts AI, Das J, Xu G, Ren G, Zhang Y, Zhang L, Yuan ZR, Tan HS, et al: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: What we do and don't know. Cell Res. 16:126–133. 2006. View Article : Google Scholar : PubMed/NCBI
35	Croxford AL, Spath S and Becher B: GM-CSF in neuroinflammation: Licensing myeloid cells for tissue damage. Trends Immunol. 36:651–662. 2015. View Article : Google Scholar : PubMed/NCBI
36	Cerwenka A, Baron JL and Lanier LL: Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo. Proc Natl Acad Sci USA. 98:11521–11526. 2001. View Article : Google Scholar : PubMed/NCBI
37	Diefenbach A, Jensen ER, Jamieson AM and Raulet DH: Rae1 and H60 ligands of the NKG2D receptor stimulate tumor immunity. Nature. 413:165–171. 2001. View Article : Google Scholar : PubMed/NCBI
38	Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, et al: Type, density and location of immune cells within human colorectal tumors predict clinical outcome. Science. 313:1960–1964. 2006. View Article : Google Scholar : PubMed/NCBI
39	Pancione M, Giordano G, Remo A, Febbraro A, Sabatino L, Manfrin E, Ceccarelli M and Colantuoni V: Immune escape mechanisms in colorectal cancer pathogenesis and liver metastasis. J Immunol Res. 2014:6868792014. View Article : Google Scholar : PubMed/NCBI
40	Alpizar YA, Chain B, Collins MK, Greenwood J, Katz D, Stauss HJ and Mitchison NA: Ten years of progress in vaccination against cancer: The need to counteract cancer evasion by dual targeting in future therapies. Cancer Immunol Immunother. 60:1127–1135. 2011. View Article : Google Scholar : PubMed/NCBI
41	Seebauer CT, Brunner S, Glockzin G, Piso P, Ruemmele P, Schlitt HJ, Geissler EK, Fichtner-Feigl S and Kesselring R: Peritoneal carcinomatosis of colorectal cancer is characterized by structural and functional reorganization of the tumor microenvironment inducing senescence and proliferation arrest in cancer cells. Oncoimmunology. 5:e12425432016. View Article : Google Scholar : PubMed/NCBI
42	Workenhe ST, Simmons G, Pol JG, Lichty BD, Halford WP and Mossman KL: Immunogenic HSV-mediated oncolysis shapes the antitumor immune response and contributes to therapeutic efficacy. Mol Ther. 22:123–131. 2014. View Article : Google Scholar : PubMed/NCBI