Application of mRNA Immunotherapy Technology in Epstein-Barr Virus-related Refractory Malignant Tumors

Summary

The purpose of this study is to evaluate the efficacy and safety of mRNA vaccine for the EBV-positive Advanced Malignant Tumors.

Timeline

Start

2023-02-08

Primary completion

2025-05-31

Completion

2025-05-31

Publications

• Background Balfour HH Jr, Schmeling DO, Grimm-Geris JM. The promise of a prophylactic Epstein-Barr virus vaccine. Pediatr Res. 2020 Jan;87(2):345-352. doi: 10.1038/s41390-019-0591-5. Epub 2019 Oct 3.
• Background Young LS, Yap LF, Murray PG. Epstein-Barr virus: more than 50 years old and still providing surprises. Nat Rev Cancer. 2016 Dec;16(12):789-802. doi: 10.1038/nrc.2016.92. Epub 2016 Sep 30.
• Background Saha A, Kaul R, Murakami M, Robertson ES. Tumor viruses and cancer biology: Modulating signaling pathways for therapeutic intervention. Cancer Biol Ther. 2010 Nov 15;10(10):961-78. doi: 10.4161/cbt.10.10.13923. Epub 2010 Nov 15.
• Background Tsao SW, Tsang CM, To KF, Lo KW. The role of Epstein-Barr virus in epithelial malignancies. J Pathol. 2015 Jan;235(2):323-33. doi: 10.1002/path.4448.
• Background ERLAY J EM, LAM F, et al. Global Cancer Observatory: cancer today . Lyon, France: International Agency for Research on Cancer 2018 https://gcoiarcfr/today (accessed November 11th, 2020). 2018.
• Background Iizasa H, Nanbo A, Nishikawa J, Jinushi M, Yoshiyama H. Epstein-Barr Virus (EBV)-associated gastric carcinoma. Viruses. 2012 Dec;4(12):3420-39. doi: 10.3390/v4123420.
• Background Qiao YW, Zhao XQ, Liu J, Yang WJ. Clinicopathological features of Epstein-Barr virus-associated gastric carcinoma: A systematic review and meta-analysis. J BUON. 2019 May-Jun;24(3):1092-1099.
• Background Ribeiro J, Malta M, Galaghar A, Afonso LP, Libanio D, Medeiros R, Dinis-Ribeiro M, Pimentel-Nunes P, Sousa H. Epstein-Barr virus is absent in gastric superficial neoplastic lesions. Virchows Arch. 2019 Dec;475(6):757-762. doi: 10.1007/s00428-019-02670-1. Epub 2019 Nov 1.
• Background Taylor GS, Jia H, Harrington K, Lee LW, Turner J, Ladell K, Price DA, Tanday M, Matthews J, Roberts C, Edwards C, McGuigan L, Hartley A, Wilson S, Hui EP, Chan AT, Rickinson AB, Steven NM. A recombinant modified vaccinia ankara vaccine encoding Epstein-Barr Virus (EBV) target antigens: a phase I trial in UK patients with EBV-positive cancer. Clin Cancer Res. 2014 Oct 1;20(19):5009-22. doi: 10.1158/1078-0432.CCR-14-1122-T. Epub 2014 Aug 14.
• Background Hui EP, Taylor GS, Jia H, Ma BB, Chan SL, Ho R, Wong WL, Wilson S, Johnson BF, Edwards C, Stocken DD, Rickinson AB, Steven NM, Chan AT. Phase I trial of recombinant modified vaccinia ankara encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients. Cancer Res. 2013 Mar 15;73(6):1676-88. doi: 10.1158/0008-5472.CAN-12-2448. Epub 2013 Jan 24.
• Background Si Y, Deng Z, Lan G, Du H, Wang Y, Si J, Wei J, Weng J, Qin Y, Huang B, Yang Y, Qin Y. The Safety and Immunological Effects of rAd5-EBV-LMP2 Vaccine in Nasopharyngeal Carcinoma Patients: A Phase I Clinical Trial and Two-Year Follow-Up. Chem Pharm Bull (Tokyo). 2016;64(8):1118-23. doi: 10.1248/cpb.c16-00114.
• Background Chia WK, Wang WW, Teo M, Tai WM, Lim WT, Tan EH, Leong SS, Sun L, Chen JJ, Gottschalk S, Toh HC. A phase II study evaluating the safety and efficacy of an adenovirus-DeltaLMP1-LMP2 transduced dendritic cell vaccine in patients with advanced metastatic nasopharyngeal carcinoma. Ann Oncol. 2012 Apr;23(4):997-1005. doi: 10.1093/annonc/mdr341. Epub 2011 Aug 4.
• Background Nishikawa J, Yoshiyama H, Iizasa H, Kanehiro Y, Nakamura M, Nishimura J, Saito M, Okamoto T, Sakai K, Suehiro Y, Yamasaki T, Oga A, Yanai H, Sakaida I. Epstein-barr virus in gastric carcinoma. Cancers (Basel). 2014 Nov 7;6(4):2259-74. doi: 10.3390/cancers6042259.
• Background Reinhard K, Rengstl B, Oehm P, Michel K, Billmeier A, Hayduk N, Klein O, Kuna K, Ouchan Y, Woll S, Christ E, Weber D, Suchan M, Bukur T, Birtel M, Jahndel V, Mroz K, Hobohm K, Kranz L, Diken M, Kuhlcke K, Tureci O, Sahin U. An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors. Science. 2020 Jan 24;367(6476):446-453. doi: 10.1126/science.aay5967. Epub 2020 Jan 2.
• Background Wang F, Qin Z, Lu H, He S, Luo J, Jin C, Song X. Clinical translation of gene medicine. J Gene Med. 2019 Jul;21(7):e3108. doi: 10.1002/jgm.3108. Epub 2019 Jul 15.
• Background Fenton OS, Kauffman KJ, McClellan RL, Kaczmarek JC, Zeng MD, Andresen JL, Rhym LH, Heartlein MW, DeRosa F, Anderson DG. Customizable Lipid Nanoparticle Materials for the Delivery of siRNAs and mRNAs. Angew Chem Int Ed Engl. 2018 Oct 8;57(41):13582-13586. doi: 10.1002/anie.201809056. Epub 2018 Sep 14.
• Background Miao L, Li L, Huang Y, Delcassian D, Chahal J, Han J, Shi Y, Sadtler K, Gao W, Lin J, Doloff JC, Langer R, Anderson DG. Delivery of mRNA vaccines with heterocyclic lipids increases anti-tumor efficacy by STING-mediated immune cell activation. Nat Biotechnol. 2019 Oct;37(10):1174-1185. doi: 10.1038/s41587-019-0247-3. Epub 2019 Sep 30.
• Background Hou X, Zhang X, Zhao W, Zeng C, Deng B, McComb DW, Du S, Zhang C, Li W, Dong Y. Author Correction: Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis. Nat Nanotechnol. 2020 Jul;15(7):615. doi: 10.1038/s41565-020-0675-8.

Drugs

Indications