Clinical Study of Therapeutic Immunological Agent for EBV-positive Advanced Malignant Tumors

Summary

To evaluate the safety of therapeutic immunological agent against EBV-positive advanced malignancies, examining the incidence, type of occurrence, and severity of adverse events in relation to the agent tested, and initially exploring the effectiveness of the immunological agent.

Timeline

Start

2023-02-08

Primary completion

2024-04-24

Completion

2027-12-31

Publications

• Background Downs-Canner SM, Meier J, Vincent BG, Serody JS. B Cell Function in the Tumor Microenvironment. Annu Rev Immunol. 2022 Apr 26;40:169-193. doi: 10.1146/annurev-immunol-101220-015603. Epub 2022 Jan 19.
• Background Choi IK, Wang Z, Ke Q, Hong M, Paul DW Jr, Fernandes SM, Hu Z, Stevens J, Guleria I, Kim HJ, Cantor H, Wucherpfennig KW, Brown JR, Ritz J, Zhang B. Mechanism of EBV inducing anti-tumour immunity and its therapeutic use. Nature. 2021 Feb;590(7844):157-162. doi: 10.1038/s41586-020-03075-w. Epub 2020 Dec 23.
• Background Klarquist J, Cross EW, Thompson SB, Willett B, Aldridge DL, Caffrey-Carr AK, Xu Z, Hunter CA, Getahun A, Kedl RM. B cells promote CD8 T cell primary and memory responses to subunit vaccines. Cell Rep. 2021 Aug 24;36(8):109591. doi: 10.1016/j.celrep.2021.109591.
• Background Schriek P, Ching AC, Moily NS, Moffat J, Beattie L, Steiner TM, Hosking LM, Thurman JM, Holers VM, Ishido S, Lahoud MH, Caminschi I, Heath WR, Mintern JD, Villadangos JA. Marginal zone B cells acquire dendritic cell functions by trogocytosis. Science. 2022 Feb 11;375(6581):eabf7470. doi: 10.1126/science.abf7470. Epub 2022 Feb 11.
• Background Rossetti RAM, Lorenzi NPC, Yokochi K, Rosa MBSF, Benevides L, Margarido PFR, Baracat EC, Carvalho JP, Villa LL, Lepique AP. B lymphocytes can be activated to act as antigen presenting cells to promote anti-tumor responses. PLoS One. 2018 Jul 5;13(7):e0199034. doi: 10.1371/journal.pone.0199034. eCollection 2018.
• Background Laurell A, Lonnemark M, Brekkan E, Magnusson A, Tolf A, Wallgren AC, Andersson B, Adamson L, Kiessling R, Karlsson-Parra A. Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma. J Immunother Cancer. 2017 Jun 20;5:52. doi: 10.1186/s40425-017-0255-0. eCollection 2017.
• Background Eagles ME, Nassiri F, Badhiwala JH, Suppiah S, Almenawer SA, Zadeh G, Aldape KD. Dendritic cell vaccines for high-grade gliomas. Ther Clin Risk Manag. 2018 Jul 26;14:1299-1313. doi: 10.2147/TCRM.S135865. eCollection 2018.
• Background Comoli P, Pedrazzoli P, Maccario R, Basso S, Carminati O, Labirio M, Schiavo R, Secondino S, Frasson C, Perotti C, Moroni M, Locatelli F, Siena S. Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein-Barr virus-targeted cytotoxic T lymphocytes. J Clin Oncol. 2005 Dec 10;23(35):8942-9. doi: 10.1200/JCO.2005.02.6195. Epub 2005 Oct 3.
• Background Bollard CM, Gottschalk S, Torrano V, Diouf O, Ku S, Hazrat Y, Carrum G, Ramos C, Fayad L, Shpall EJ, Pro B, Liu H, Wu MF, Lee D, Sheehan AM, Zu Y, Gee AP, Brenner MK, Heslop HE, Rooney CM. Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins. J Clin Oncol. 2014 Mar 10;32(8):798-808. doi: 10.1200/JCO.2013.51.5304. Epub 2013 Dec 16.
• Background Lopez-Chavez A, Thomas A, Rajan A, Raffeld M, Morrow B, Kelly R, Carter CA, Guha U, Killian K, Lau CC, Abdullaev Z, Xi L, Pack S, Meltzer PS, Corless CL, Sandler A, Beadling C, Warrick A, Liewehr DJ, Steinberg SM, Berman A, Doyle A, Szabo E, Wang Y, Giaccone G. Molecular profiling and targeted therapy for advanced thoracic malignancies: a biomarker-derived, multiarm, multihistology phase II basket trial. J Clin Oncol. 2015 Mar 20;33(9):1000-7. doi: 10.1200/JCO.2014.58.2007. Epub 2015 Feb 9.
• Background Cunanan KM, Gonen M, Shen R, Hyman DM, Riely GJ, Begg CB, Iasonos A. Basket Trials in Oncology: A Trade-Off Between Complexity and Efficiency. J Clin Oncol. 2017 Jan 20;35(3):271-273. doi: 10.1200/JCO.2016.69.9751. Epub 2016 Nov 28. No abstract available.
• Background Cho J, Kang MS, Kim KM. Epstein-Barr Virus-Associated Gastric Carcinoma and Specific Features of the Accompanying Immune Response. J Gastric Cancer. 2016 Mar;16(1):1-7. doi: 10.5230/jgc.2016.16.1.1. Epub 2016 Mar 31.
• Background Young LS, Dawson CW. Epstein-Barr virus and nasopharyngeal carcinoma. Chin J Cancer. 2014 Dec;33(12):581-90. doi: 10.5732/cjc.014.10197. Epub 2014 Nov 21.
• Background Kanakry JA, Ambinder RF. EBV-related lymphomas: new approaches to treatment. Curr Treat Options Oncol. 2013 Jun;14(2):224-36. doi: 10.1007/s11864-013-0231-y.
• Background Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. doi: 10.1016/S0140-6736(10)61121-X. Epub 2010 Aug 19.
• Background Bekoz H, Karadurmus N, Paydas S, Turker A, Toptas T, Firatli Tuglular T, Sonmez M, Gulbas Z, Tekgunduz E, Kaya AH, Ozbalak M, Tastemir N, Kaynar L, Yildirim R, Karadogan I, Arat M, Pepedil Tanrikulu F, Ozkocaman V, Abali H, Turgut M, Kurt Yuksel M, Ozcan M, Dogu MH, Kabukcu Hacioglu S, Barista I, Demirkaya M, Koseoglu FD, Toprak SK, Yilmaz M, Demirkurek HC, Demirkol O, Ferhanoglu B. Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience. Ann Oncol. 2017 Oct 1;28(10):2496-2502. doi: 10.1093/annonc/mdx341.
• Background Kfoury M, Disdero V, Vicier C, Le Saux O, Gougis P, Sajous C, Vignot S. [Immune checkpoints inhibitors: Recent data from ASCO's meeting 2017 and perspectives]. Bull Cancer. 2018 Jul-Aug;105(7-8):686-695. doi: 10.1016/j.bulcan.2018.04.011. Epub 2018 Jun 20. French.
• Background Holko P, Kawalec P. Economic evaluation of sipuleucel-T immunotherapy in castration-resistant prostate cancer. Expert Rev Anticancer Ther. 2014 Jan;14(1):63-73. doi: 10.1586/14737140.2014.856270.
• Background Tanyi JL, Bobisse S, Ophir E, Tuyaerts S, Roberti A, Genolet R, Baumgartner P, Stevenson BJ, Iseli C, Dangaj D, Czerniecki B, Semilietof A, Racle J, Michel A, Xenarios I, Chiang C, Monos DS, Torigian DA, Nisenbaum HL, Michielin O, June CH, Levine BL, Powell DJ Jr, Gfeller D, Mick R, Dafni U, Zoete V, Harari A, Coukos G, Kandalaft LE. Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer. Sci Transl Med. 2018 Apr 11;10(436):eaao5931. doi: 10.1126/scitranslmed.aao5931.
• Background Liau LM, Ashkan K, Tran DD, Campian JL, Trusheim JE, Cobbs CS, Heth JA, Salacz M, Taylor S, D'Andre SD, Iwamoto FM, Dropcho EJ, Moshel YA, Walter KA, Pillainayagam CP, Aiken R, Chaudhary R, Goldlust SA, Bota DA, Duic P, Grewal J, Elinzano H, Toms SA, Lillehei KO, Mikkelsen T, Walbert T, Abram SR, Brenner AJ, Brem S, Ewend MG, Khagi S, Portnow J, Kim LJ, Loudon WG, Thompson RC, Avigan DE, Fink KL, Geoffroy FJ, Lindhorst S, Lutzky J, Sloan AE, Schackert G, Krex D, Meisel HJ, Wu J, Davis RP, Duma C, Etame AB, Mathieu D, Kesari S, Piccioni D, Westphal M, Baskin DS, New PZ, Lacroix M, May SA, Pluard TJ, Tse V, Green RM, Villano JL, Pearlman M, Petrecca K, Schulder M, Taylor LP, Maida AE, Prins RM, Cloughesy TF, Mulholland P, Bosch ML. First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma. J Transl Med. 2018 May 29;16(1):142. doi: 10.1186/s12967-018-1507-6.
• Background Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.

Drugs

Indications