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Lin W, Zhao Y, Zhong L. Current strategies of virotherapy in clinical trials for cancer treatment. J Med Virol. 2021;93(8):4668-4692doi: 10.1002/jmv.26947.
Lin, W., Zhao, Y., & Zhong, L. (2021). Current strategies of virotherapy in clinical trials for cancer treatment. Journal of medical virology, 93(8), 4668-4692. https://doi.org/10.1002/jmv.26947
Lin, Weijian, et al. "Current strategies of virotherapy in clinical trials for cancer treatment." Journal of medical virology vol. 93,8 (2021): 4668-4692. doi: https://doi.org/10.1002/jmv.26947
Lin W, Zhao Y, Zhong L. Current strategies of virotherapy in clinical trials for cancer treatment. J Med Virol. 2021 Aug;93(8):4668-4692. doi: 10.1002/jmv.26947. Epub 2021 Apr 23. PMID: 33738818.
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J Med Virol. 2021 Aug;93(8):4668-4692. doi: 10.1002/jmv.26947. Epub 2021 Apr 23.

Current strategies of virotherapy in clinical trials for cancer treatment.

Journal of medical virology

Weijian Lin, Yongxiang Zhao, Liping Zhong

Affiliations

  1. National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Bio-targeting Theranostics, Guangxi Medical University, Nanning, China.

PMID: 33738818 DOI: 10.1002/jmv.26947

Abstract

As a novel immune-active agent for cancer treatment, viruses have the ability of infecting and replicating in tumor cells. The safety and efficacy of viruses has been tested and confirmed in preclinical and clinical trials. In the last decade, virotherapy has been adopted as a monotherapy or combined therapy with immunotherapy, chemotherapy, or radiotherapy, showing promising outcomes against cancer. In this review, the current strategies of viruses used in clinical trials are classified and described. Besides this, the challenge and future prospects of virotherapy in the management for cancer patients are discussed in this review.

© 2021 Wiley Periodicals LLC.

Keywords: cancer treatment; chemotherapy; clinical trials; immunotherapy; radiotherapy; virotherapy; virus

References

  1. Gujar S , Pol JG , Kroemer G . Heating it up: oncolytic viruses make tumors 'hot' and suitable for checkpoint blockade immunotherapies. Oncoimmunology. 2018;7(8):e1442169. https://doi.org/10.1080/2162402X.2018.144216 - PubMed
  2. Bommareddy PK , Shettigar M , Kaufman HL . Integrating oncolytic viruses in combination cancer immunotherapy. Nat Rev Immunol. 2018;18(8):498-513. https://doi.org/10.1038/s41577-018-0014-6 - PubMed
  3. Masoud SJ , Hu JB , Beasley GM , Stewart JH , Mosca PJ .Efficacy of talimogene laherparepvec (T-VEC) therapy in patients with in-transit melanoma metastasis decreases with increasing lesion size. Ann Surg Oncol. 2019;26(13):4633-4641. https://doi.org/10.1245/s10434-019-07691-3 - PubMed
  4. Tejada S , Alonso M , Patino A , Fueyo J , Gomez-Manzano C , Diez-Valle R . Phase I trial of DNX-2401 for diffuse intrinsic pontine glioma newly diagnosed in pediatric patients. Neurosurgery. 2018;83(5):1050-1056. https://doi.org/10.1093/neuros/nyx507 - PubMed
  5. Leber MF , Neault S , Jirovec E , et al. Engineering and combining oncolytic measles virus for cancer therapy. Cytokine Growth Factor Rev. 2020;56:39-48. https://doi.org/10.1016/j.cytogfr.2020.07.005 - PubMed
  6. Chen CY , Hutzen B , Wedekind MF , Cripe TP . Oncolytic virus and PD-1/PD-L1 blockade combination therapy. Oncolytic Virother. 2018;7:65-77. https://doi.org/10.2147/OV.S145532 - PubMed
  7. Lan Q , Xia S , Wang Q , et al. Development of oncolytic virotherapy: from genetic modification to combination therapy. Front Med. 2020;14(2):160-184. https://doi.org/10.1007/s11684-020-0750-4 - PubMed
  8. Strong JE , Coffey MC , Tang D , Sabinin P , Lee PW . The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus. EMBO J. 1998;17(12):3351-3362. https://doi.org/10.1093/emboj/17.12.3351 - PubMed
  9. Maitra R , Ghalib MH , Goel S . Reovirus: a targeted therapeutic-progress and potential. Mol Cancer Res. 2012;10(12):1514-1525. https://doi.org/10.1158/1541-7786.MCR-12-0157 - PubMed
  10. Gollamudi R , Ghalib MH , Desai KK , et al. Intravenous administration of Reolysin, a live replication competent RNA virus is safe in patients with advanced solid tumors. Invest New Drugs. 2010;28(5):641-649. https://doi.org/10.1007/s10637-009-9279-8 - PubMed
  11. Morris DG , Feng X , DiFrancesco LM , et al. REO-001: a phase I trial of percutaneous intralesional administration of reovirus type 3 dearing (Reolysin(R)) in patients with advanced solid tumors. Invest New Drugs. 2013;31(3):696-706. https://doi.org/10.1007/s10637-012-9865-z - PubMed
  12. Kicielinski KP , Chiocca EA , Yu JS , Gill GM , Coffey M , Markert JM . Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults. Mol Ther. 2014;22(5):1056-1062. https://doi.org/10.1038/mt.2014.21 - PubMed
  13. Sborov DW , Nuovo GJ , Stiff A , et al. A phase I trial of single-agent reolysin in patients with relapsed multiple myeloma. Clin Cancer Res. 2014;20(23):5946-5955. https://doi.org/10.1158/1078-0432.CCR-14-1404 - PubMed
  14. Kolb EA , Sampson V , Stabley D , et al. A phase I trial and viral clearance study of reovirus (Reolysin) in children with relapsed or refractory extra-cranial solid tumors: a Children's Oncology Group Phase I Consortium report. Pediatr Blood Cancer. 2015;62(5):751-758. https://doi.org/10.1002/pbc.25464 - PubMed
  15. Xiao C , Bator CM , Bowman VD , et al. Interaction of coxsackievirus A21 with its cellular receptor, ICAM-1. J Virol. 2001;75(5):2444-2451. https://doi.org/10.1128/JVI.75.5.2444-2451.2001 - PubMed
  16. Xiao C , Bator-Kelly CM , Rieder E , et al. The crystal structure of coxsackievirus A21 and its interaction with ICAM-1. Structure. 2005;13(7):1019-1033. https://doi.org/10.1016/j.str.2005.04.011 - PubMed
  17. Johansson ES , Xing L , Cheng RH , Shafren DR . Enhanced cellular receptor usage by a bioselected variant of coxsackievirus a21. J Virol. 2004;78(22):12603-12612. https://doi.org/10.1128/JVI.78.22.12603-12612.2004 - PubMed
  18. Au GG , Lincz LF , Enno A , Shafren DR . Oncolytic coxsackievirus A21 as a novel therapy for multiple myeloma. Br J Haematol. 2007;137(2):133-141. https://doi.org/10.1111/j.1365-2141.2007.06550.x - PubMed
  19. Reddy PS , Burroughs KD , Hales LM , et al. Seneca Valley virus, a systemically deliverable oncolytic picornavirus, and the treatment of neuroendocrine cancers. J Natl Cancer Inst. 2007;99(21):1623-1633. https://doi.org/10.1093/jnci/djm198 - PubMed
  20. Hales LM , Knowles NJ , Reddy PS , Xu L , Hay C , Hallenbeck PL . Complete genome sequence analysis of Seneca Valley virus-001, a novel oncolytic picornavirus. J Gen Virol. 2008;89(Pt 5):1265-1275. https://doi.org/10.1099/vir.0.83570-0 - PubMed
  21. Cao L , Zhang R , Liu T , et al. Seneca Valley virus attachment and uncoating mediated by its receptor anthrax toxin receptor 1. Proc Natl Acad Sci USA. 2018;115(51):13087-13092. https://doi.org/10.1073/pnas.1814309115 - PubMed
  22. Jayawardena N , Burga LN , Easingwood RA , Takizawa Y , Wolf M , Bostina M . Structural basis for anthrax toxin receptor 1 recognition by Seneca Valley Virus. Proc Natl Acad Sci USA. 2018;115(46):E10934-E10940. https://doi.org/10.1073/pnas.1810664115 - PubMed
  23. Miles LA , Burga LN , Gardner EE , Bostina M , Poirier JT , Rudin CM . Anthrax toxin receptor 1 is the cellular receptor for Seneca Valley virus. J Clin Invest. 2017;127(8):2957-2967. https://doi.org/10.1172/JCI93472 - PubMed
  24. Rudin CM , Poirier JT , Senzer NN , et al. Phase I clinical study of Seneca Valley Virus (SVV-001), a replication-competent picornavirus, in advanced solid tumors with neuroendocrine features. Clin Cancer Res. 2011;17(4):888-895. https://doi.org/10.1158/1078-0432.CCR-10-1706 - PubMed
  25. Burke MJ , Ahern C , Weigel BJ , et al. Phase I trial of Seneca Valley virus (NTX-010) in children with relapsed/refractory solid tumors: a report of the Children's Oncology Group. Pediatr Blood Cancer. 2015;62(5):743-750. https://doi.org/10.1002/pbc.25269 - PubMed
  26. Kawashima T , Kagawa S , Kobayashi N , et al. Telomerase-specific replication-selective virotherapy for human cancer. Clin Cancer Res. 2004;10(1 Pt 1):285-292. https://doi.org/10.1158/1078-0432.ccr-1075-3 - PubMed
  27. Sasaki T , Tazawa H , Hasei J , et al. Preclinical evaluation of telomerase-specific oncolytic virotherapy for human bone and soft tissue sarcomas. Clin Cancer Res. 2011;17(7):1828-1838. https://doi.org/10.1158/1078-0432.CCR-10-2066 - PubMed
  28. Hashimoto Y , Watanabe Y , Shirakiya Y , et al. Establishment of biological and pharmacokinetic assays of telomerase-specific replication-selective adenovirus. Cancer Sci. 2008;99(2):385-390. https://doi.org/10.1111/j.1349-7006.2007.00665.x - PubMed
  29. Nemunaitis J , Tong AW , Nemunaitis M , et al. A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors. Mol Ther. 2010;18(2):429-434. https://doi.org/10.1038/mt.2009.262 - PubMed
  30. Fueyo J , Alemany R , Gomez-Manzano C , et al. Preclinical characterization of the antiglioma activity of a tropism-enhanced adenovirus targeted to the retinoblastoma pathway. J Natl Cancer Inst. 2003;95(9):652-660. https://doi.org/10.1093/jnci/95.9.652 - PubMed
  31. Fueyo J , Gomez-Manzano C , Alemany R , et al. A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene. 2000;19(1):2-12. https://doi.org/10.1038/sj.onc.1203251 - PubMed
  32. Lang FF , Conrad C , Gomez-Manzano C , et al. Phase I Study of DNX-2401 (Delta-24-RGD) oncolytic adenovirus: replication and immunotherapeutic effects in recurrent malignant glioma. J Clin Oncol. 2018;36(14):1419-1427. https://doi.org/10.1200/JCO.2017.75.8219 - PubMed
  33. Suzuki K , Fueyo J , Krasnykh V , Reynolds PN , Curiel DT , Alemany R . A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency. Clin Cancer Res. 2001;7(1):120-126. - PubMed
  34. Cascallo M , Alonso MM , Rojas JJ , Perez-Gimenez A , Fueyo J , Alemany R . Systemic toxicity-efficacy profile of ICOVIR-5, a potent and selective oncolytic adenovirus based on the pRB pathway. Mol Ther. 2007;15(9):1607-1615. https://doi.org/10.1038/sj.mt.6300239 - PubMed
  35. García M , Moreno R , Gil-Martin M , et al. A phase 1 trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients. Hum Gene Ther. 2019;30(3):352-364. https://doi.org/10.1089/hum.2018.107 - PubMed
  36. Eissa IR , Naoe Y , Bustos-Villalobos I , et al. Genomic signature of the natural oncolytic herpes simplex virus HF10 and its therapeutic role in preclinical and clinical trials. Front Oncol. 2017;7:149. https://doi.org/10.3389/fonc.2017.00149 - PubMed
  37. Nakao A , Kasuya H , Sahin TT , et al. A phase I dose-escalation clinical trial of intraoperative direct intratumoral injection of HF10 oncolytic virus in non-resectable patients with advanced pancreatic cancer. Cancer Gene Ther. 2011;18(3):167-175. https://doi.org/10.1038/cgt.2010.65 - PubMed
  38. Ackermann M , Chou J , Sarmiento M , Lerner RA , Roizman B . Identification by antibody to a synthetic peptide of a protein specified by a diploid gene located in the terminal repeats of the L component of herpes simplex virus genome. J Virol. 1986;58(3):843-850. https://doi.org/10.1128/JVI.58.3.843-850.1986 - PubMed
  39. Chou J , Kern ER , Whitley RJ , Roizman B . Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture. Science. 1990;250(4985):1262-1266. https://doi.org/10.1126/science.2173860 - PubMed
  40. Streby KA , Geller JI , Currier MA , et al. Intratumoral injection of HSV1716, an oncolytic herpes virus, is safe and shows evidence of immune response and viral replication in young cancer patients. Clin Cancer Res. 2017;23(14):3566-3574. https://doi.org/10.1158/1078-0432.CCR-16-2900 - PubMed
  41. Streby KA , Currier MA , Triplet M , et al. First-in-human intravenous seprehvir in young cancer patients: a phase 1 clinical trial. Mol Ther. 2019;27(11):1930-1938. https://doi.org/10.1016/j.ymthe.2019.08.020 - PubMed
  42. Lauer UM , Schell M , Beil J , et al. Phase I study of oncolytic vaccinia virus GL-ONC1 in patients with peritoneal carcinomatosis. Clin Cancer Res. 2018;24(18):4388-4398. https://doi.org/10.1158/1078-0432.CCR-18-0244 - PubMed
  43. Lawler SE , Speranza MC , Cho CF , Chiocca EA . Oncolytic viruses in cancer treatment: a review. JAMA Oncol. 2017;3(6):841-849. https://doi.org/10.1001/jamaoncol.2016.2064 - PubMed
  44. Raja J , Ludwig JM , Gettinger SN , Schalper KA , Kim HS . Oncolytic virus immunotherapy: future prospects for oncology. J Immunother Cancer. 2018;6(1):140. https://doi.org/10.1186/s40425-018-0458-z - PubMed
  45. Neuman E , Flemington EK , Sellers WR , Kaelin WG Jr. Transcription of the E2F-1 gene is rendered cell cycle dependent by E2F DNA-binding sites within its promoter. Mol Cell Biol. 1994;14(10):6607-6615. https://doi.org/10.1128/mcb.14.10.6607 - PubMed
  46. Ramesh N , Ge Y , Ennist DL , et al. CG0070, a conditionally replicating granulocyte macrophage colony-stimulating factor-armed oncolytic adenovirus for the treatment of bladder cancer. Clin Cancer Res. 2006;12(1):305-313. https://doi.org/10.1158/1078-0432.CCR-05-1059 - PubMed
  47. Burke JM , Lamm DL , Meng MV , et al. A first in human phase 1 study of CG0070, a GM-CSF expressing oncolytic adenovirus, for the treatment of nonmuscle invasive bladder cancer. J Urol. 2012;188(6):2391-2397. https://doi.org/10.1016/j.juro.2012.07.097 - PubMed
  48. Packiam VT , Lamm DL , Barocas DA , et al. An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non-muscle-invasive bladder cancer: Interim results. Urol Oncol. 2018;36(10):440-447. https://doi.org/10.1016/j.urolonc.2017.07.005 - PubMed
  49. Dinney CPN , Fisher MB , Navai N , et al. Phase I trial of intravesical recombinant adenovirus mediated interferon-alpha2b formulated in Syn3 for Bacillus Calmette-Guerin failures in nonmuscle invasive bladder cancer. J Urol. 2013;190(3):850-856. https://doi.org/10.1016/j.juro.2013.03.030 - PubMed
  50. Shore ND , Boorjian SA , Canter DJ , et al. Intravesical rAd-IFNalpha/Syn3 for patients with high-grade, bacillus calmette-guerin-refractory or relapsed non-muscle-invasive bladder cancer: a phase II randomized study. J Clin Oncol. 2017;35(30):3410-3416. https://doi.org/10.1200/JCO.2017.72.3064 - PubMed
  51. Poppers J , Mulvey M , Khoo D , Mohr I . Inhibition of PKR activation by the proline-rich RNA binding domain of the herpes simplex virus type 1 Us11 protein. J Virol. 2000;74(23):11215-11221. https://doi.org/10.1128/jvi.74.23.11215-11221.2000 - PubMed
  52. He B , Gross M , Roizman B . The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc Natl Acad Sci USA. 1997;94(3):843-848. https://doi.org/10.1073/pnas.94.3.843 - PubMed
  53. Toda M , Martuza RL , Rabkin SD . Tumor growth inhibition by intratumoral inoculation of defective herpes simplex virus vectors expressing granulocyte-macrophage colony-stimulating factor. Mol Ther. 2000;2(4):324-329. https://doi.org/10.1006/mthe.2000.0130 - PubMed
  54. Hu JCC , Coffin RS , Davis CJ , et al. A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res. 2006;12(22):6737-6747. https://doi.org/10.1158/1078-0432.CCR-06-0759 - PubMed
  55. Kaufman HL , Kim DW , DeRaffele G , Mitcham J , Coffin RS , Kim-Schulze S . Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding GM-CSF in patients with stage IIIc and IV melanoma. Ann Surg Oncol. 2010;17(3):718-730. https://doi.org/10.1245/s10434-009-0809-6 - PubMed
  56. Senzer NN , Kaufman HL , Amatruda T , et al. Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol. 2009;27(34):5763-5771. https://doi.org/10.1200/JCO.2009.24.3675 - PubMed
  57. Andtbacka RHI , Ross M , Puzanov I , et al. Patterns of clinical response with talimogene laherparepvec (T-VEC) in patients with melanoma treated in the optim phase III clinical trial. Ann Surg Oncol. 2016;23(13):4169-4177. https://doi.org/10.1245/s10434-016-5286-0 - PubMed
  58. Mastrangelo MJ , Maguire HC Jr. , Eisenlohr LC , et al. Intratumoral recombinant GM-CSF-encoding virus as gene therapy in patients with cutaneous melanoma. Cancer Gene Ther. 1999;6(5):409-422. https://doi.org/10.1038/sj.cgt.7700066 - PubMed
  59. Kim JH , Oh JY , Park BH , et al. Systemic armed oncolytic and immunologic therapy for cancer with JX-594, a targeted poxvirus expressing GM-CSF. Mol Ther. 2006;14(3):361-370. https://doi.org/10.1016/j.ymthe.2006.05.008 - PubMed
  60. Breitbach CJ , Burke J , Jonker D , et al. Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature. 2011;477(7362):99-102. https://doi.org/10.1038/nature10358 - PubMed
  61. Kirn DH , Thorne SH . Targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic class for cancer. Nat Rev Cancer. 2009;9(1):64-71. https://doi.org/10.1038/nrc2545 - PubMed
  62. Yang H , Kim SK , Kim M , et al. Antiviral chemotherapy facilitates control of poxvirus infections through inhibition of cellular signal transduction. J Clin Invest. 2005;115(2):379-387. https://doi.org/10.1172/JCI23220 - PubMed
  63. Hwang TH , Moon A , Burke J , et al. A mechanistic proof-of-concept clinical trial with JX-594, a targeted multi-mechanistic oncolytic poxvirus, in patients with metastatic melanoma. Mol Ther. 2011;19(10):1913-1922. https://doi.org/10.1038/mt.2011.132 - PubMed
  64. Park SH , Breitbach CJ , Lee J , et al. Phase 1b trial of biweekly intravenous pexa-vec (JX-594), an oncolytic and immunotherapeutic vaccinia virus in colorectal cancer. Mol Ther. 2015;23(9):1532-1540. https://doi.org/10.1038/mt.2015.109 - PubMed
  65. Heo J , Reid T , Ruo L , et al. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat Med. 2013;19(3):329-336. https://doi.org/10.1038/nm.3089 - PubMed
  66. Breitbach CJ , Moon A , Burke J , Hwang TH , Kirn DH . A phase 2, open-label, randomized study of pexa-vec (JX-594) administered by intratumoral injection in patients with unresectable primary hepatocellular carcinoma. Methods Mol Biol. 2015;1317:343-357. https://doi.org/10.1007/978-1-4939-2727-2_19 - PubMed
  67. Harrop R , Chu F , Gabrail N , Srinivas S , Blount D , Ferrari A . Vaccination of castration-resistant prostate cancer patients with TroVax (MVA-5T4) in combination with docetaxel: a randomized phase II trial. Cancer Immunol Immunother. 2013;62(9):1511-1520. https://doi.org/10.1007/s00262-013-1457-z - PubMed
  68. Harrop R , Shingler WH , McDonald M , et al. MVA-5T4-induced immune responses are an early marker of efficacy in renal cancer patients. Cancer Immunol Immunother. 2011;60(6):829-837. https://doi.org/10.1007/s00262-011-0993-7 - PubMed
  69. Gulley JL , Borre M , Vogelzang NJ , et al. Phase III Trial of PROSTVAC in asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37(13):1051-1061. https://doi.org/10.1200/JCO.18.02031 - PubMed
  70. Galanis E , Hartmann LC , Cliby WA , et al. Phase I trial of intraperitoneal administration of an oncolytic measles virus strain engineered to express carcinoembryonic antigen for recurrent ovarian cancer. Cancer Res. 2010;70(3):875-882. https://doi.org/10.1158/0008-5472.CAN-09-2762 - PubMed
  71. Suominen E , Toivonen R , Grenman R , Savontaus M . Head and neck cancer cells are efficiently infected by Ad5/35 hybrid virus. J Gene Med. 2006;8(10):1223-1231. https://doi.org/10.1002/jgm.957 - PubMed
  72. Kuryk L , Moller AW . Chimeric oncolytic Ad5/3 virus replicates and lyses ovarian cancer cells through desmoglein-2 cell entry receptor. J Med Virol. 2020;92(8):1309-1315. https://doi.org/10.1002/jmv.25677 - PubMed
  73. Stepanenko AA , Chekhonin VP . A compendium of adenovirus genetic modifications for enhanced replication, oncolysis, and tumor immunosurveillance in cancer therapy. Gene. 2018;679:11-18. https://doi.org/10.1016/j.gene.2018.08.069 - PubMed
  74. Man YKS , Davies JA , Coughlan L , et al. The novel oncolytic adenoviral mutant Ad5-3Delta-A20T retargeted to alphavbeta6 integrins efficiently eliminates pancreatic cancer cells. Mol Cancer Ther. 2018;17(2):575-587. https://doi.org/10.1158/1535-7163.MCT-17-0671 - PubMed
  75. Wu T , Mo Y , Wu C . Prognostic values of CEA, CA19-9, and CA72-4 in patients with stages I-III colorectal cancer. Int J Clin Exp Pathol. 2020;13(7):1608-1614. - PubMed
  76. Song X , Liang B , Wang C , Shi S . Clinical value of color Doppler ultrasound combined with serum CA153, CEA and TSGF detection in the diagnosis of breast cancer. Exp Ther Med. 2020;20(2):1822-1828. https://doi.org/10.3892/etm.2020.8868 - PubMed
  77. Huang G , Chen R , Lu N , Chen Q , Lv W , Li B . Combined evaluation of preoperative serum CEA and CA125 as an independent prognostic biomarker in patients with early-stage cervical adenocarcinoma. Onco Targets Ther. 2020;13:5155-5164. https://doi.org/10.2147/OTT.S250614 - PubMed
  78. Gabitzsch ES , Xu Y , Balint JP Jr , Hartman ZC , Lyerly HK , Jones FR . Anti-tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA. Cancer Immunol Immunother. 2010;59(7):1131-1135. https://doi.org/10.1007/s00262-010-0847-8 - PubMed
  79. Osada T , Yang XY , Hartman ZC , et al. Optimization of vaccine responses with an E1, E2b and E3-deleted Ad5 vector circumvents pre-existing anti-vector immunity. Cancer Gene Ther. 2009;16(9):673-682. https://doi.org/10.1038/cgt.2009.17 - PubMed
  80. Morse MA , Chaudhry A , Gabitzsch ES , et al. Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients. Cancer Immunol Immunother. 2013;62(8):1293-1301. https://doi.org/10.1007/s00262-013-1400-3 - PubMed
  81. Peng KW , Facteau S , Wegman T , O'Kane D , Russell SJ . Non-invasive in vivo monitoring of trackable viruses expressing soluble marker peptides. Nat Med. 2002;8(5):527-531. https://doi.org/10.1038/nm0502-527 - PubMed
  82. Peng KW , TenEyck CJ , Galanis E , Kalli KR , Hartmann LC , Russell SJ . Intraperitoneal therapy of ovarian cancer using an engineered measles virus. Cancer Res. 2002;62(16):4656-4662. - PubMed
  83. Zhang SC , Cai WS , Zhang Y , Jiang KL , Zhang KR , Wang WL . Engineered measles virus Edmonston strain used as a novel oncolytic viral system against human neuroblastoma through a CD46 and nectin 4-independent pathway. Cancer Lett. 2012;325(2):227-237. https://doi.org/10.1016/j.canlet.2012.07.008 - PubMed
  84. Allen C , Opyrchal M , Aderca I , et al. Oncolytic measles virus strains have significant antitumor activity against glioma stem cells. Gene Ther. 2013;20(4):444-449. https://doi.org/10.1038/gt.2012.62 - PubMed
  85. Msaouel P , Iankov ID , Allen C , et al. Engineered measles virus as a novel oncolytic therapy against prostate cancer. Prostate. 2009;69(1):82-91. https://doi.org/10.1002/pros.20857 - PubMed
  86. Rodriguez JF , Eggener SE . Prostate cancer and the evolving role of biomarkers in screening and diagnosis. Radiol Clin North Am. 2018;56(2):187-196. https://doi.org/10.1016/j.rcl.2017.10.002 - PubMed
  87. Liu J , Li Y , Yang D , Yang C , Mao L . Current state of biomarkers for the diagnosis and assessment of treatment efficacy of prostate cancer. Discov Med. 2019;27(150):235-243. - PubMed
  88. DiPaola R , Plante M , Kaufman H , et al. A phase I trial of pox PSA vaccines (PROSTVAC-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM) in patients with prostate cancer. J Transl Med. 2006;4:1. https://doi.org/10.1186/1479-5876-4-1 - PubMed
  89. Arlen PM , Skarupa L , Pazdur M , et al. Clinical safety of a viral vector based prostate cancer vaccine strategy. J Urol. 2007;178(4 Pt 1):1515-1520. https://doi.org/10.1016/j.juro.2007.05.117 - PubMed
  90. Gulley JL , Arlen PM , Madan RA , et al. Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol Immunother. 2010;59(5):663-674. https://doi.org/10.1007/s00262-009-0782-8 - PubMed
  91. Kantoff PW , Schuetz TJ , Blumenstein BA , et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010;28(7):1099-1105. https://doi.org/10.1200/JCO.2009.25.0597 - PubMed
  92. Buchbinder EI , Desai A . CTLA-4 and PD-1 Pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39(1):98-106. https://doi.org/10.1097/COC.0000000000000239 - PubMed
  93. Intlekofer AM , Thompson CB . At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. J Leukoc Biol. 2013;94(1):25-39. https://doi.org/10.1189/jlb.1212621 - PubMed
  94. Constantinidou A , Alifieris C , Trafalis DT . Targeting programmed cell death −1 (PD-1) and ligand (PD-L1): a new era in cancer active immunotherapy. Pharmacol Ther. 2019;194:84-106. https://doi.org/10.1016/j.pharmthera.2018.09.008 - PubMed
  95. Rosato PC , Wijeyesinghe S , Stolley JM , et al. Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy. Nat Commun. 2019;10(1):567. https://doi.org/10.1038/s41467-019-08534-1 - PubMed
  96. Goepfert K , Dinsart C , Rommelaere J , Foerster F , Moehler M . Rational combination of parvovirus H1 with CTLA-4 and PD-1 checkpoint inhibitors dampens the tumor induced immune silencing. Front Oncol. 2019;9:425. https://doi.org/10.3389/fonc.2019.00425 - PubMed
  97. Oseledchyk A , Ricca JM , Gigoux M , et al. Lysis-independent potentiation of immune checkpoint blockade by oncolytic virus. Oncotarget. 2018;9(47):28702-28716. https://doi.org/10.18632/oncotarget.25614 - PubMed
  98. Ranki T , Joensuu T , Jäger E , et al. Local treatment of a pleural mesothelioma tumor with ONCOS-102 induces a systemic antitumor CD8(+) T-cell response, prominent infiltration of CD8(+) lymphocytes and Th1 type polarization. Oncoimmunology. 2014;3(10):e958937. https://doi.org/10.4161/21624011.2014.958937 - PubMed
  99. Vassilev L , Ranki T , Joensuu T , et al. Repeated intratumoral administration of ONCOS-102 leads to systemic antitumor CD8(+) T-cell response and robust cellular and transcriptional immune activation at tumor site in a patient with ovarian cancer. Oncoimmunology. 2015;4(7):e1017702. https://doi.org/10.1080/2162402X.2015.1017702 - PubMed
  100. Kuryk L , Haavisto E , Garofalo M , et al. Synergistic anti-tumor efficacy of immunogenic adenovirus ONCOS-102 (Ad5/3-D24-GM-CSF) and standard of care chemotherapy in preclinical mesothelioma model. Int J Cancer. 2016;139(8):1883-1893. https://doi.org/10.1002/ijc.30228 - PubMed
  101. 34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 2. Journal for ImmunoTherapy of Cancer. 2019;7(1):283. https://doi.org/10.1186/s40425-019-0764-0 - PubMed
  102. Aiken R , Chen C , Cloughesy T , et al. ATIM-33. Interim results of a phase ii multi-center study of oncolytic adenovirus Dnx-2401 with pembrolizumab for recurrent glioblastoma; captive study (KEYNOTE-192). Neuro-Oncology. 2019;21(Suppl_6):vi8-vi9. https://doi.org/10.1093/neuonc/noz175.032 - PubMed
  103. Ribas A , Hamid O , Daud A , et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA. 2016;315(15):1600-1609. https://doi.org/10.1001/jama.2016.4059 - PubMed
  104. Robert C , Ribas A , Schachter J , et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol. 2019;20(9):1239-1251. https://doi.org/10.1016/S1470-2045(19)30388-2 - PubMed
  105. Robert C , Schachter J , Long GV , et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521-2532. https://doi.org/10.1056/NEJMoa1503093 - PubMed
  106. Ribas A , Dummer R , Puzanov I , et al. Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy. Cell. 2017;170(6):1109-19 e10. https://doi.org/10.1016/j.cell.2017.08.027 - PubMed
  107. Subudhi SK , Aparicio A , Gao J , et al. Clonal expansion of CD8 T cells in the systemic circulation precedes development of ipilimumab-induced toxicities. Proc Natl Acad Sci USA. 2016;113(42):11919-11924. https://doi.org/10.1073/pnas.1611421113 - PubMed
  108. Puzanov I , Milhem MM , Minor D , et al. Talimogene laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma. J Clin Oncol. 2016;34(22):2619-2626. https://doi.org/10.1200/JCO.2016.67.1529 - PubMed
  109. Chesney J , Puzanov I , Collichio F , et al. Patterns of response with talimogene laherparepvec in combination with ipilimumab or ipilimumab alone in metastatic unresectable melanoma. Br J Cancer. 2019;121(5):417-420. https://doi.org/10.1038/s41416-019-0530-6 - PubMed
  110. Mahalingam D , Wilkinson GA , Eng KH , et al. Pembrolizumab in combination with the oncolytic virus pelareorep and chemotherapy in patients with advanced pancreatic adenocarcinoma: a phase Ib study. Clin Cancer Res. 2020;26(1):71-81. https://doi.org/10.1158/1078-0432.CCR-19-2078 - PubMed
  111. Wilson JM . Gendicine: the first commercial gene therapy product. Hum Gene Ther. 2005;16(9):1014-1015. https://doi.org/10.1089/hum.2005.16.1014 - PubMed
  112. Wang D , Wang K , Cai Y . An overview of development in gene therapeutics in China. Gene Ther. 2020;27(7-8):338-348. https://doi.org/10.1038/s41434-020-0163-7 - PubMed
  113. Xie Q , Liang BL , Wu YH , et al. Synergistic anticancer effect of rAd/P53 combined with 5-fluorouracil or iodized oil in the early therapeutic response of human colon cancer in vivo. Gene. 2012;499(2):303-308. https://doi.org/10.1016/j.gene.2012.02.007 - PubMed
  114. Xie Q , Wu MY , Zhang DX , et al. Synergistic anticancer effect of exogenous wild-type p53 gene combined with 5-FU in human colon cancer resistant to 5-FU in vivo. World J Gastroenterol. 2016;22(32):7342-7352. https://doi.org/10.3748/wjg.v22.i32.7342 - PubMed
  115. Liu YG , Zheng XL , Liu FM . The mechanism and inhibitory effect of recombinant human P53 adenovirus injection combined with paclitaxel on human cervical cancer cell HeLa. Eur Rev Med Pharmacol Sci. 2015;19(6):1037-1042. - PubMed
  116. Xie YS , Zhang YH , Liu SP , et al. Synergistic gastric cancer inhibition by chemogenetherapy with recombinant human adenovirus p53 and epirubicin: an in vitro and in vivo study. Oncol Rep. 2010;24(6):1613-1620. - PubMed
  117. Xiao J , Zhou J , Liang L , et al. Sensitivity of ASPP and P-gp to neoadjuvant chemotherapy combined with gene therapy in locally advanced cervical cancer. J BUON. 2019;24(3):967-974. - PubMed
  118. Li Y , Li LJ , Wang LJ , et al. Selective intra-arterial infusion of rAd-p53 with chemotherapy for advanced oral cancer: a randomized clinical trial. BMC Med. 2014;12:16. https://doi.org/10.1186/1741-7015-12-16 - PubMed
  119. Xia Y , Du Z , Wang X , Li X . Treatment of uterine sarcoma with rAd-p53 (Gendicine) followed by chemotherapy: clinical study of TP53 gene therapy. Hum Gene Ther. 2018;29(2):242-250. https://doi.org/10.1089/hum.2017.206 - PubMed
  120. Shimoyama S , Goshima F , Teshigahara O , et al. Enhanced efficacy of herpes simplex virus mutant HF10 combined with paclitaxel in peritoneal cancer dissemination models. Hepatogastroenterology. 2007;54(76):1038-1042. - PubMed
  121. Tanaka R , Goshima F , Esaki S , et al. The efficacy of combination therapy with oncolytic herpes simplex virus HF10 and dacarbazine in a mouse melanoma model. Am J Cancer Res. 2017;7(8):1693-1703. - PubMed
  122. Esaki S , Goshima F , Kimura H , Murakami S , Nishiyama Y . Enhanced antitumoral activity of oncolytic herpes simplex virus with gemcitabine using colorectal tumor models. Int J Cancer. 2013;132(7):1592-1601. https://doi.org/10.1002/ijc.27823 - PubMed
  123. Hirooka Y , Kasuya H , Ishikawa T , et al. A phase I clinical trial of EUS-guided intratumoral injection of the oncolytic virus, HF10 for unresectable locally advanced pancreatic cancer. BMC Cancer. 2018;18(1):596. https://doi.org/10.1186/s12885-018-4453-z - PubMed
  124. Harrington KJ , Hingorani M , Tanay MA , et al. Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck. Clin Cancer Res. 2010;16(15):4005-4015. https://doi.org/10.1158/1078-0432.CCR-10-0196 - PubMed
  125. Goel S , Ocean AJ , Parakrama RY , et al. Elucidation of Pelareorep pharmacodynamics in a phase I trial in patients with KRAS-mutated colorectal cancer. Mol Cancer Ther. 2020;19(5):1148-1156. https://doi.org/10.1158/1535-7163.MCT-19-1117 - PubMed
  126. Comins C , Spicer J , Protheroe A , et al. REO-10: a phase I study of intravenous reovirus and docetaxel in patients with advanced cancer. Clin Cancer Res. 2010;16(22):5564-5572. https://doi.org/10.1158/1078-0432.CCR-10-1233 - PubMed
  127. Lolkema MP , Arkenau HT , Harrington K , et al. A phase I study of the combination of intravenous reovirus type 3 Dearing and gemcitabine in patients with advanced cancer. Clin Cancer Res. 2011;17(3):581-588. https://doi.org/10.1158/1078-0432.CCR-10-2159 - PubMed
  128. Karapanagiotou EM , Roulstone V , Twigger K , et al. Phase I/II trial of carboplatin and paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with advanced malignancies. Clin Cancer Res. 2012;18(7):2080-2089. https://doi.org/10.1158/1078-0432.CCR-11-2181 - PubMed
  129. Cohn DE , Sill MW , Walker JL , et al. Randomized phase IIB evaluation of weekly paclitaxel versus weekly paclitaxel with oncolytic reovirus (Reolysin(R)) in recurrent ovarian, tubal, or peritoneal cancer. An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2017;146(3):477-483. https://doi.org/10.1016/j.ygyno.2017.07.135 - PubMed
  130. Bernstein V , Ellard SL , Dent SF , et al. A randomized phase II study of weekly paclitaxel with or without pelareorep in patients with metastatic breast cancer: final analysis of Canadian Cancer Trials Group IND.213. Breast Cancer Res Treat. 2018;167(2):485-493. https://doi.org/10.1007/s10549-017-4538-4 - PubMed
  131. Roulstone V , Khan K , Pandha HS , et al. Phase I trial of cyclophosphamide as an immune modulator for optimizing oncolytic reovirus delivery to solid tumors. Clin Cancer Res. 2015;21(6):1305-1312. https://doi.org/10.1158/1078-0432.CCR-14-1770 - PubMed
  132. Bradbury PA , Morris DG , Nicholas G , et al. Canadian Cancer Trials Group (CCTG) IND211: a randomized trial of pelareorep (Reolysin) in patients with previously treated advanced or metastatic non-small cell lung cancer receiving standard salvage therapy. Lung Cancer. 2018;120:142-148. https://doi.org/10.1016/j.lungcan.2018.03.005 - PubMed
  133. Brenner DJ , Ward JF . Constraints on energy deposition and target size of multiply damaged sites associated with DNA double-strand breaks. Int J Radiat Biol. 1992;61(6):737-748. https://doi.org/10.1080/09553009214551591 - PubMed
  134. Mole RH . Whole body irradiation; radiobiology or medicine? Br J Radiol. 1953;26(305):234-241. https://doi.org/10.1259/0007-1285-26-305-234 - PubMed
  135. Okuma K , Yamashita H , Niibe Y , Hayakawa K , Nakagawa K . Abscopal effect of radiation on lung metastases of hepatocellular carcinoma: a case report. J Med Case Rep. 2011;5:111. https://doi.org/10.1186/1752-1947-5-111 - PubMed
  136. Welsh JW , Tang C , de Groot P , et al. Phase II trial of ipilimumab with stereotactic radiation therapy for metastatic disease: outcomes, toxicities, and low-dose radiation-related abscopal responses. Cancer Immunol Res. 2019;7(12):1903-1909. https://doi.org/10.1158/2326-6066.CIR-18-0793 - PubMed
  137. Chandra RA , Wilhite TJ , Balboni TA , et al. A systematic evaluation of abscopal responses following radiotherapy in patients with metastatic melanoma treated with ipilimumab. Oncoimmunology. 2015;4(11):e1046028. https://doi.org/10.1080/2162402X.2015.1046028 - PubMed
  138. Chen RF , Li YY , Li LT , Cheng Q , Jiang G , Zheng JN . Novel oncolytic adenovirus sensitizes renal cell carcinoma cells to radiotherapy via mitochondrial apoptotic cell death. Mol Med Rep. 2015;11(3):2141-2146. https://doi.org/10.3892/mmr.2014.2987 - PubMed
  139. Zhao MJ , Song YF , Niu HT , et al. Adenovirus-mediated downregulation of the ubiquitin ligase RNF8 sensitizes bladder cancer to radiotherapy. Oncotarget. 2016;7(8):8956-8967. https://doi.org/10.18632/oncotarget.6909 - PubMed
  140. Gao H , Zhang X , Ding Y , Qiu R , Hong Y , Chen W . Synergistic suppression effect on tumor growth of colorectal cancer by combining radiotherapy with a trail-armed oncolytic adenovirus. Technol Cancer Res Treat. 2019;18:1533033819853290. https://doi.org/10.1177/1533033819853290 - PubMed
  141. Kyula JN , Khan AA , Mansfield D , et al. Synergistic cytotoxicity of radiation and oncolytic Lister strain vaccinia in (V600D/E)BRAF mutant melanoma depends on JNK and TNF-alpha signaling. Oncogene. 2014;33(13):1700-1712. https://doi.org/10.1038/onc.2013.112 - PubMed
  142. Chiocca EA , Aguilar LK , Bell SD , et al. Phase IB study of gene-mediated cytotoxic immunotherapy adjuvant to up-front surgery and intensive timing radiation for malignant glioma. J Clin Oncol. 2011;29(27):3611-3619. https://doi.org/10.1200/JCO.2011.35.5222 - PubMed
  143. Wheeler LA , Manzanera AG , Bell SD , et al. Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma. Neuro Oncol. 2016;18(8):1137-1145. https://doi.org/10.1093/neuonc/now002 - PubMed
  144. Westphal M , Ylä-Herttuala S , Martin J , et al. Adenovirus-mediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir for patients with operable high-grade glioma (ASPECT): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14(9):823-833. https://doi.org/10.1016/S1470-2045(13)70274-2 - PubMed
  145. Kieran MW , Goumnerova L , Manley P , et al. Phase I study of gene-mediated cytotoxic immunotherapy with AdV-tk as adjuvant to surgery and radiation for pediatric malignant glioma and recurrent ependymoma. Neuro Oncol. 2019;21(4):537-546. https://doi.org/10.1093/neuonc/noy202 - PubMed
  146. Mineta T , Rabkin SD , Yazaki T , Hunter WD , Martuza RL . Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas. Nat Med. 1995;1(9):938-943. https://doi.org/10.1038/nm0995-938 - PubMed
  147. Markert JM , Liechty PG , Wang W , et al. Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. Mol Ther. 2009;17(1):199-207. https://doi.org/10.1038/mt.2008.228 - PubMed
  148. Aghi MK , Chiocca EA . Phase ib trial of oncolytic herpes virus G207 shows safety of multiple injections and documents viral replication. Mol Ther. 2009;17(1):8-9. https://doi.org/10.1038/mt.2008.275 - PubMed
  149. Markert JM , Razdan SN , Kuo HC , et al. A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses. Mol Ther. 2014;22(5):1048-1055. https://doi.org/10.1038/mt.2014.22 - PubMed
  150. McEntee G , Kyula JN , Mansfield D , et al. Enhanced cytotoxicity of reovirus and radiotherapy in melanoma cells is mediated through increased viral replication and mitochondrial apoptotic signalling. Oncotarget. 2016;7(30):48517-48532. https://doi.org/10.18632/oncotarget.10365 - PubMed
  151. Harrington KJ , Karapanagiotou EM , Roulstone V , et al. Two-stage phase I dose-escalation study of intratumoral reovirus type 3 dearing and palliative radiotherapy in patients with advanced cancers. Clin Cancer Res. 2010;16(11):3067-3077. https://doi.org/10.1158/1078-0432.CCR-10-0054 - PubMed
  152. Minev BR , Lander E , Feller JF , et al. First-in-human study of TK-positive oncolytic vaccinia virus delivered by adipose stromal vascular fraction cells. J Transl Med. 2019;17(1):271. https://doi.org/10.1186/s12967-019-2011-3 - PubMed
  153. Russell SJ , Federspiel MJ , Peng KW , et al. Remission of disseminated cancer after systemic oncolytic virotherapy. Mayo Clin Proc. 2014;89(7):926-933. https://doi.org/10.1016/j.mayocp.2014.04.003 - PubMed
  154. Dispenzieri A , Tong C , LaPlant B , et al. Phase I trial of systemic administration of Edmonston strain of measles virus genetically engineered to express the sodium iodide symporter in patients with recurrent or refractory multiple myeloma. Leukemia. 2017;31(12):2791-2798. https://doi.org/10.1038/leu.2017.120 - PubMed
  155. Kanerva A , Zinn KR , Chaudhuri TR , et al. Enhanced therapeutic efficacy for ovarian cancer with a serotype 3 receptor-targeted oncolytic adenovirus. Mol Ther. 2003;8(3):449-458. https://doi.org/10.1016/s1525-0016(03)00200-4 - PubMed
  156. Ong HT , Timm MM , Greipp PR , et al. Oncolytic measles virus targets high CD46 expression on multiple myeloma cells. Exp Hematol. 2006;34(6):713-720. https://doi.org/10.1016/j.exphem.2006.03.002 - PubMed
  157. Parato KA , Breitbach CJ , Le Boeuf F , et al. The oncolytic poxvirus JX-594 selectively replicates in and destroys cancer cells driven by genetic pathways commonly activated in cancers. Mol Ther. 2012;20(4):749-758. https://doi.org/10.1038/mt.2011.276 - PubMed

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