drugset / Trial / NCT03044743
PD-1 Knockout EBV-CTLs for Advanced Stage Epstein-Barr Virus (EBV) Associated Malignancies
NaSingle-groupOpen-labelTreatment
Summary
This study will evaluate the safety of PD-1 knockout EBV-CTL cells in treating EBV (Epstein-Barr virus) positive advanced stage malignancies. Blood samples will also be collected for research purposes.
Timeline
- Start
- 2017-04-07
- Primary completion
- 2020-03
- Completion
- 2022-03
Publications
- Background Kim SY, Park C, Kim HJ, Park J, Hwang J, Kim JI, Choi MG, Kim S, Kim KM, Kang MS. Deregulation of immune response genes in patients with Epstein-Barr virus-associated gastric cancer and outcomes. Gastroenterology. 2015 Jan;148(1):137-147.e9. doi: 10.1053/j.gastro.2014.09.020. Epub 2014 Sep 22.
- Background Quan L, Chen X, Liu A, Zhang Y, Guo X, Yan S, Liu Y. PD-1 Blockade Can Restore Functions of T-Cells in Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma In Vitro. PLoS One. 2015 Sep 11;10(9):e0136476. doi: 10.1371/journal.pone.0136476. eCollection 2015.
- Background Louis CU, Straathof K, Bollard CM, Ennamuri S, Gerken C, Lopez TT, Huls MH, Sheehan A, Wu MF, Liu H, Gee A, Brenner MK, Rooney CM, Heslop HE, Gottschalk S. Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma. J Immunother. 2010 Nov-Dec;33(9):983-90. doi: 10.1097/CJI.0b013e3181f3cbf4.
- Background Lloyd A, Vickery ON, Laugel B. Beyond the antigen receptor: editing the genome of T-cells for cancer adoptive cellular therapies. Front Immunol. 2013 Aug 5;4:221. doi: 10.3389/fimmu.2013.00221. eCollection 2013.
- Background Su S, Hu B, Shao J, Shen B, Du J, Du Y, Zhou J, Yu L, Zhang L, Chen F, Sha H, Cheng L, Meng F, Zou Z, Huang X, Liu B. CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients. Sci Rep. 2016 Jan 28;6:20070. doi: 10.1038/srep20070.
- Background Mali P, Esvelt KM, Church GM. Cas9 as a versatile tool for engineering biology. Nat Methods. 2013 Oct;10(10):957-63. doi: 10.1038/nmeth.2649.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Background | Cyclophosphamide | Other / unclassified | 300 mg/m2 | Intravenous |
| Background | Fludarabine | Small molecule | 30 mg/m2 | Intravenous |
| Background | aldesleukin | Protein / enzyme biologic | 4e+06 iu | Intravenous |