Research advance of oncolytic virus in liver cancer

Abstract

Abstract: Liver cancer is a major global health concern whose clinical treatment means are limited, facing a series of challenges such as high postoperative recurrence rates, high transplant failure rates and resistance to chemotherapy drugs, and the overall clinical benefit is unsatisfactory. In recent years, with the rapid development of immunotherapy, major breakthroughs have been achieved in the treatment of multiple malignant tumors. As a new biological immunotherapy agent, oncolytic virus (OV) kills tumors by highly selective infecting and lysing tumor cells, activating the body's immune response, improving the tumor microenvironment and other mechanisms, and numerous clinical studies have been carried out in the treatment of liver cancer. The preliminary data show an encouraging application prospects. Herein, this review systematically introduces the mechanism of action of OV while comprehensively summarizes the latest clinical research progress of OV in liver cancer, Particularly,we emphasize the innovative products of OV in the treatment of liver cancer and its research and development design strategy, as well as sorts out the combination therapy of OV, which will provide potential directions for the future treatment of liver cancer with OV.

Key words: Oncolytic virus, Liver cancer, Hepatocellular carcinoma, Immunotherapy

Xiang Guilin, Song Shuhui, Duan Shijie, Fang Hong, Tang Yu, Liu Funan. Research advance of oncolytic virus in liver cancer[J]. Electronic Journal of Liver Tumor, 2024, 11(4): 13-18.

References

[1] BRAY F, LAVERSANNE M, SUNG H, et al.Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263.
[2] ZHOU J, SUN H, WANG Z, et al.Guidelines for the diagnosis and treatment of primary liver cancer (2022 Edition)[J]. Liver Cancer, 2023, 12(5): 405-444.
[3] LLOVET J M, RICCI S, MAZZAFERRO V, et al.Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med, 2008, 359(4): 378-390.
[4] CHENG A L, KANG Y K, CHEN Z, et al.Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phaseⅢ randomised, double-blind, placebo-controlled trial[J]. Lancet Oncol, 2009, 10(1): 25-34.
[5] CHENG A L, GUAN Z, CHEN Z, et al.Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: subset analyses of the phase Ⅲ Sorafenib Asia-Pacific trial[J]. Eur J Cancer, 2012, 48(10): 1452-1465.
[6] FINN R S, QIN S, IKEDA M, et al.Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma[J]. N Engl J Med, 2020, 382(20): 1894-1905.
[7] WEN F, ZHENG H, ZHANG P, et al.Atezolizumab and bevacizumab combination compared with sorafenib as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma: a cost-effectiveness analysis in China and the United States[J]. Liver Int, 2021, 41(5): 1097-1104.
[8] GALLE P R, FINN R S, QIN S, et al.Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial[J]. Lancet Oncol, 2021, 22(7): 991-1001.
[9] KAUFMAN H L, KOHLHAPP F J, ZLOZA A.Oncolytic viruses: a new class of immunotherapy drugs[J]. Nat Rev Drug Discov, 2015, 14(9): 642-662.
[10] BOMMAREDDY P K, SHETTIGAR M, KAUFMAN H L.Integrating oncolytic viruses in combination cancer immunotherapy[J]. Nat Rev Immunol, 2018, 18(8): 498-513.
[11] HEMMINKI O, DOS SANTOS J M, HEMMINKI A. Oncolytic viruses for cancer immunotherapy[J]. J Hematol Oncol, 2020, 13(1): 84.
[12] ANDTBACKA R H, KAUFMAN H L, COLLICHIO F, et al.Talimogene laherparepvec improves durable response rate in patients with advanced melanoma[J]. J Clin Oncol, 2015, 33(25): 2780-2788.
[13] TODO T, ITO H, INO Y, et al.Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: a phase 2 trial[J]. Nat Med, 2022, 28(8): 1630-1639.
[14] PARK B H, HWANG T, LIU T C, et al.Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phaseⅠ trial[J]. Lancet Oncol, 2008, 9(6): 533-542.
[15] BREITBACH C J, ARULANANDAM R, DE SILVA N, et al.Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans[J]. Cancer Res, 2013, 73(4): 1265-1275.
[16] ZHANG Y, QIAN L, CHEN K, et al.Intraperitoneal oncolytic virotherapy for patients with malignant ascites: Characterization of clinical efficacy and antitumor immune response[J]. Mol Ther Oncolytics, 2022, 25: 31-42.
[17] HE C, ZHANG Y, LIN X.Increased overall survival and decreased cancer-specific mortality in patients with hepatocellular carcinoma treated by transarterial chemoembolization and human adenovirus type-5 combination therapy: a competing risk analysis[J]. J Gastrointest Surg, 2018, 22(6): 989-997.
[18] HECHT J R, PLESS M, CUBILLO A, et al.Early safety from a phase I, multicenter, open-label clinical trial of talimogene laherparepvec (T-VEC) injected (inj) into liver tumors in combination with pembrolizumab (pem)[J]. J Clin Oncol, 2020, 38(Suppl 5): 3015.
[19] DöRIG R E, MARCIL A, CHOPRA A, et al. The human CD46 molecule is a receptor for measles virus (Edmonston strain)[J]. Cell, 1993, 75(2): 295-305.
[20] YU Z, CHAN M K, P O C, et al. Enhanced nectin-1 expression and herpes oncolytic sensitivity in highly migratory and invasive carcinoma[J]. Clin Cancer Res, 2005, 11(13): 4889-4897.
[21] BERGELSON J M, CUNNINGHAM J A, DROGUETT G, et al.Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5[J]. Science, 1997, 275(5304): 1320-1323.
[22] LI X, SUN X, WANG B, et al.Oncolytic virus-based hepatocellular carcinoma treatment: Current status, intravenous delivery strategies, and emerging combination therapeutic solutions[J]. Asian J Pharm Sci, 2023, 18(1): 100771.
[23] LIN J, SUN S, ZHAO K, et al.Oncolytic Parapoxvirus induces Gasdermin E-mediated pyroptosis and activates antitumor immunity[J]. Nat Commun, 2023, 14(1): 224.
[24] HARRINGTON K, FREEMAN D J, KELLY B, et al.Optimizing oncolytic virotherapy in cancer treatment[J]. Nat Rev Drug Discov, 2019, 18(9): 689-706.
[25] MA J, RAMACHANDRAN M, JIN C, et al.Characterization of virus-mediated immunogenic cancer cell death and the consequences for oncolytic virus-based immunotherapy of cancer[J]. Cell Death Dis, 2020, 11(1): 48.
[26] KIM M, OSBORNE N R, ZENG W, et al.Herpes simplex virus antigens directly activate NK cells via TLR2, thus facilitating their presentation to CD4 T lymphocytes[J]. J Immunol, 2012, 188(9): 4158-4170.
[27] JIN M Z, JIN W L.The updated landscape of tumor microenvironment and drug repurposing[J]. Signal Transduct Target Ther, 2020, 5(1): 166.
[28] VITALE I, MANIC G, COUSSENS L M, et al.Macrophages and metabolism in the tumor microenvironment[J]. Cell Metab, 2019, 30(1): 36-50.
[29] JIANG H, RIVERA-MOLINA Y, GOMEZ-MANZANO C, et al.Oncolytic adenovirus and tumor-targeting immune modulatory therapy improve autologous cancer vaccination[J]. Cancer Res, 2017, 77(14): 3894-3907.
[30] KANAYA N, KURODA S, KAKIUCHI Y, et al.Immune modulation by telomerase-specific oncolytic adenovirus synergistically enhances antitumor efficacy with anti-pd1 antibody[J]. Mol Ther, 2020, 28(3): 794-804.
[31] LI Z, LAI X, FU S, et al.Immunogenic cell death activates the tumor immune microenvironment to boost the immunotherapy efficiency[J]. Adv Sci (Weinh), 2022, 9(22): e2201734.
[32] LEE Y S, LEE W S, KIM C W, et al.Oncolytic vaccinia virus reinvigorates peritoneal immunity and cooperates with immune checkpoint inhibitor to suppress peritoneal carcinomatosis in colon cancer[J]. J Immunother Cancer, 2020, 8(2): e000857.
[33] YOO J Y, KIM J H, KWON Y G, et al.VEGF-specific short hairpin RNA-expressing oncolytic adenovirus elicits potent inhibition of angiogenesis and tumor growth[J]. Mol Ther, 2007, 15(2): 295-302.
[34] HEO J, REID T, RUO L, et al.Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer[J]. Nat Med, 2013, 19(3): 329-336.
[35] MOEHLER M, HEO J, LEE H C, et al.Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter phase Ⅱb trial (TRAVERSE)[J]. Oncoimmunology, 2019, 8(8): 1615817.
[36] HUSSEINI F, DELORD J P, FOURNEL-FEDERICO C, et al.Vectorized gene therapy of liver tumors: proof-of-concept of TG4023 (MVA-FCU1) in combination with flucytosine[J]. Ann Oncol, 2017, 28(1): 169-174.
[37] 夏忠军,常建华,张力,等. 基因工程腺病毒(H101)瘤内注射联合化疗治疗头颈部及食管鳞癌的Ⅲ期临床研究[J]. 癌症,2004(12):1666-1670.
[38] GARBER K.China approves world's first oncolytic virus therapy for cancer treatment[J]. J Natl Cancer Inst, 2006, 98(5): 298-300.
[39] WANG T, ZANG C, ZHANG Y, et al.Efficacy of oncolytic virus combined with HAIC of mFOLFOX for IMCC: A single-center, single-arm, prospective study[J]. J Clin Oncol, 2024, 42(Suppl 16) : e16265.
[40] HEO J, LIANG J D, KIM C W, et al.940P Dose-escalation trial of OBP-301, novel telomerase-specific oncolytic virus in advanced hepatocellular carcinoma[J]. Ann Oncol, 2021, 32(Suppl 5): S823.
[41] SHEN Y, LIANG X, JIN X, et al. Clinical outcomes from a phase Ⅰ clinical trial of a novel oncolytic virus VG161 in patients with hepatocellular carcinoma (HCC) refractory after 2 prior lines of therapy including checkpoint inhibitors (CPI)[J]. J Clin Oncol, 2024, 42 Suppl: 4105.
[42] ZHANG J, LAI W, LI Q, et al.A novel oncolytic adenovirus targeting Wnt signaling effectively inhibits cancer-stem like cell growth via metastasis, apoptosis and autophagy in HCC models[J]. Biochem Biophys Res Commun, 2017, 491(2): 469-477.
[43] XIAO S, LIU Z, DENG R, et al.Aptamer-mediated gene therapy enhanced antitumor activity against human hepatocellular carcinoma in vitro and in vivo[J]. J Control Release, 2017, 258: 130-145.
[44] LIANG Y, WANG B, CHEN Q, et al.Systemic delivery of glycosylated-PEG-masked oncolytic virus enhances targeting of antitumor immuno-virotherapy and modulates T and NK cell infiltration[J]. Theranostics, 2023, 13(15): 5452-5468.
[45] NAGALO B M, ZHOU Y, LOEUILLARD E J, et al.Characterization of Morreton virus as an oncolytic virotherapy platform for liver cancers[J]. Hepatology, 2023, 77(6): 1943-1957.
[46] SAMSON A, BENTHAM M J, SCOTT K, et al.Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer[J]. Gut, 2018, 67(3): 562-573.
[47] ONG H T, FEDERSPIEL M J, GUO C M, et al.Systemically delivered measles virus-infected mesenchymal stem cells can evade host immunity to inhibit liver cancer growth[J]. J Hepatol, 2013, 59(5): 999-1006.
[48] CHEN L, NIU Y, SUN J, et al.Oncolytic activity of wild-type newcastle disease virus HK84 against hepatocellular carcinoma associated with activation of typeⅠ interferon signaling[J]. J Clin Transl Hepatol, 2022, 10(2): 284-296.
[49] ZHOU P, WANG X, XING M, et al.Intratumoral delivery of a novel oncolytic adenovirus encoding human antibody against PD-1 elicits enhanced antitumor efficacy[J]. Mol Ther Oncolytics, 2022, 25: 236-248.
[50] DAI F, ZHANG P B, FENG Q, et al.Cytokine-induced killer cells carrying recombinant oncolytic adenovirus expressing p21Ras scFv inhibited liver cancer[J]. J Cancer, 2021, 12(9): 2768-2776.
[51] CHO E, AN M H, LEE Y S, et al.Development of chimeric antigen receptor (CAR)-T cells targeting A56 viral protein implanted by oncolytic virus[J]. iScience, 2024, 27(3): 109256.
[52] SOLIMAN H, HOGUE D, HAN H, et al.Oncolytic T-VEC virotherapy plus neoadjuvant chemotherapy in nonmetastatic triple-negative breast cancer: a phase 2 trial[J]. Nat Med, 2023, 29(2): 450-457.
[53] DUMMER R, GYORKI D E, HYNGSTROM J, et al.Neoadjuvant talimogene laherparepvec plus surgery versus surgery alone for resectable stageⅢB-ⅣM1a melanoma: a randomized, open-label, phase 2 trial[J]. Nat Med, 2021, 27(10): 1789-1796.
[54] THOMAS R J, BARTEE E.The use of oncolytic virotherapy in the neoadjuvant setting[J]. J Immunother Cancer, 2022, 10(4): e004462.