drugset / Trial / NCT05587543
Clinical Study on the EBV CAR-T /TCR-T Cells in the Treatment of Nasopharyngeal Carcinoma
Non-randomizedParallel-groupOpen-labelTreatment
Summary
This study was a single-arm, open-label, "3 + 3" dose-escalation Exploratory research. The patients were divided into two groups: EBV TCR-T-cell Group and EBV CAR-T-cell group. The EBV CAR-T-treated group received three progressively increasing dose levels (3.0 × 106 cells/kg, 9.0 × 106 cells/kg, 1.5 × 107 cells/kg) of EBV CAR-T-cell therapy; The EBV TCR-T-cell group received three progressively increasing doses (5.0 × 106 cells/kg, 1.5 × 107 cells/kg, 3.0 × 107 cells/kg) of EBV TCR-T-cell therapy.
Timeline
- Start
- 2022-12-28
- Primary completion
- 2027-10
- Completion
- 2030-10
Publications
- Results Taylor GS, Long HM, Brooks JM, Rickinson AB, Hislop AD. The immunology of Epstein-Barr virus-induced disease. Annu Rev Immunol. 2015;33:787-821. doi: 10.1146/annurev-immunol-032414-112326. Epub 2015 Feb 11.
- Results Dalton T, Doubrovina E, Pankov D, Reynolds R, Scholze H, Selvakumar A, Vizconde T, Savalia B, Dyomin V, Weigel C, Oakes CC, Alonso A, Elemento O, Pan H, Phillip JM, O'Reilly RJ, Gewurz BE, Cesarman E, Giulino-Roth L. Epigenetic reprogramming sensitizes immunologically silent EBV+ lymphomas to virus-directed immunotherapy. Blood. 2020 May 21;135(21):1870-1881. doi: 10.1182/blood.2019004126.
- Results Castillo JJ, Beltran BE, Miranda RN, Paydas S, Winer ES, Butera JN. Epstein-barr virus-positive diffuse large B-cell lymphoma of the elderly: what we know so far. Oncologist. 2011;16(1):87-96. doi: 10.1634/theoncologist.2010-0213. Epub 2011 Jan 6.
- Results Dojcinov SD, Fend F, Quintanilla-Martinez L. EBV-Positive Lymphoproliferations of B- T- and NK-Cell Derivation in Non-Immunocompromised Hosts. Pathogens. 2018 Mar 7;7(1):28. doi: 10.3390/pathogens7010028.
- Results Thompson MP, Kurzrock R. Epstein-Barr virus and cancer. Clin Cancer Res. 2004 Feb 1;10(3):803-21. doi: 10.1158/1078-0432.ccr-0670-3.
- Results Kimura H, Fujiwara S. Overview of EBV-Associated T/NK-Cell Lymphoproliferative Diseases. Front Pediatr. 2019 Jan 4;6:417. doi: 10.3389/fped.2018.00417. eCollection 2018.
- Results Healy JA, Dave SS. The Role of EBV in the Pathogenesis of Diffuse Large B Cell Lymphoma. Curr Top Microbiol Immunol. 2015;390(Pt 1):315-37. doi: 10.1007/978-3-319-22822-8_13.
- Results Mao Y, Zhang DW, Zhu H, Lin H, Xiong L, Cao Q, Liu Y, Li QD, Xu JR, Xu LF, Chen RJ. LMP1 and LMP2A are potential prognostic markers of extranodal NK/T-cell lymphoma, nasal type (ENKTL). Diagn Pathol. 2012 Dec 13;7:178. doi: 10.1186/1746-1596-7-178.
- Results Wang ZY, Liu QF, Wang H, Jin J, Wang WH, Wang SL, Song YW, Liu YP, Fang H, Ren H, Wu RY, Chen B, Zhang XM, Lu NN, Zhou LQ, Li YX. Clinical implications of plasma Epstein-Barr virus DNA in early-stage extranodal nasal-type NK/T-cell lymphoma patients receiving primary radiotherapy. Blood. 2012 Sep 6;120(10):2003-10. doi: 10.1182/blood-2012-06-435024. Epub 2012 Jul 23.
- Results Cho SG, Kim N, Sohn HJ, Lee SK, Oh ST, Lee HJ, Cho HI, Yim HW, Jung SE, Park G, Oh JH, Choi BO, Kim SW, Kim SW, Chung NG, Lee JW, Hong YS, Kim TG. Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs. Mol Ther. 2015 Aug;23(8):1401-1409. doi: 10.1038/mt.2015.91. Epub 2015 May 28.
- Results Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
- Results Chen YP, Chan ATC, Le QT, Blanchard P, Sun Y, Ma J. Nasopharyngeal carcinoma. Lancet. 2019 Jul 6;394(10192):64-80. doi: 10.1016/S0140-6736(19)30956-0. Epub 2019 Jun 6.
- Results Wang L, Tian WD, Xu X, Nie B, Lu J, Liu X, Zhang B, Dong Q, Sunwoo JB, Li G, Li XP. Epstein-Barr virus nuclear antigen 1 (EBNA1) protein induction of epithelial-mesenchymal transition in nasopharyngeal carcinoma cells. Cancer. 2014 Feb 1;120(3):363-72. doi: 10.1002/cncr.28418. Epub 2013 Nov 4.
- Results Zhu S, Chen J, Xiong Y, Kamara S, Gu M, Tang W, Chen S, Dong H, Xue X, Zheng ZM, Zhang L. Novel EBV LMP-2-affibody and affitoxin in molecular imaging and targeted therapy of nasopharyngeal carcinoma. PLoS Pathog. 2020 Jan 6;16(1):e1008223. doi: 10.1371/journal.ppat.1008223. eCollection 2020 Jan.
- Results Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.
- Results Lee AW, Ng WT, Chan LL, Hung WM, Chan CC, Sze HC, Chan OS, Chang AT, Yeung RM. Evolution of treatment for nasopharyngeal cancer--success and setback in the intensity-modulated radiotherapy era. Radiother Oncol. 2014 Mar;110(3):377-84. doi: 10.1016/j.radonc.2014.02.003. Epub 2014 Mar 11.
- Results Chen L, Hu CS, Chen XZ, Hu GQ, Cheng ZB, Sun Y, Li WX, Chen YY, Xie FY, Liang SB, Chen Y, Xu TT, Li B, Long GX, Wang SY, Zheng BM, Guo Y, Sun Y, Mao YP, Tang LL, Chen YM, Liu MZ, Ma J. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012 Feb;13(2):163-71. doi: 10.1016/S1470-2045(11)70320-5. Epub 2011 Dec 7.
- Results Oliva M, Huang SH, Taylor R, Su J, Xu W, Hansen AR, Jang R, Bayley A, Hosni A, Giuliani M, Ringash J, Bratman SV, Cho J, Irish J, Waldron J, Weinreb I, Kim J, O'Sullivan B, Siu LL, Spreafico A. Impact of cumulative cisplatin dose and adjuvant chemotherapy in locally-advanced nasopharyngeal carcinoma treated with definitive chemoradiotherapy. Oral Oncol. 2020 Jun;105:104666. doi: 10.1016/j.oraloncology.2020.104666. Epub 2020 Apr 6.
- Results Zhang E, Gu J, Xu H. Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors. Mol Cancer. 2018 Jan 12;17(1):7. doi: 10.1186/s12943-018-0759-3.
- Results Castellarin M, Watanabe K, June CH, Kloss CC, Posey AD Jr. Driving cars to the clinic for solid tumors. Gene Ther. 2018 Jun;25(3):165-175. doi: 10.1038/s41434-018-0007-x. Epub 2018 Jun 7.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | CAR | Cell therapy | 3e+06 cells/kg | — |
| Subject | CAR | Cell therapy | 9e+06 cells/kg | — |
| Subject | CAR | Cell therapy | 1.5e+07 cells/kg | — |
| Subject | TCR | Cell therapy | 5e+06 cells/kg | — |
| Subject | TCR | Cell therapy | 1.5e+07 cells/kg | — |
| Subject | TCR | Cell therapy | 3e+07 cells/kg | — |