Adoptive Transfer of Epstein-Barr Virus (EBV) Nuclear Antigen 1-Specific T Cells As Treatment for EBV Reactivation and Lymphoproliferative Disorders After Allogeneic Stem-Cell Transplantation

被引：217

作者：

Icheva, Vanya ^{[1
]}

Kayser, Simone ^{[1
]}

Wolff, Daniel ^{[4
]}

Tuve, Sebastian ^{[5
]}

Kyzirakos, Christina ^{[2
]}

Bethge, Wolfgang ^{[3
]}

Greil, Johann ^{[6
]}

Albert, Michael H. ^{[7
]}

Schwinger, Wolfgang ^{[9
]}

Nathrath, Michaela ^{[8
]}

Schumm, Michael ^{[1
]}

Stevanovic, Stefan ^{[2
]}

Handgretinger, Rupert ^{[1
]}

Lang, Peter ^{[1
]}

Feuchtinger, Tobias ^{[1
]}

机构：

[1] Univ Childrens Hosp Tubingen, Tubingen, Germany

[2] Univ Tubingen, D-72076 Tubingen, Germany

[3] Univ Tubingen Hosp, Tubingen, Germany

[4] Univ Hosp Regensburg, Regensburg, Germany

[5] Univ Hosp Dresden, Dresden, Germany

[6] Univ Childrens Hosp Heidelberg, Heidelberg, Germany

[7] Haunersches Childrens Hosp Munchen, Munich, Germany

[8] Helmholtz Zentrum Munchen, Munich, Germany

[9] Univ Childrens Hosp Graz, Graz, Austria

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2013年 / 31卷 / 01期

关键词：

ADENOVIRUS INFECTION; VIRAL-INFECTIONS; DISEASE; RECIPIENTS; IMMUNOTHERAPY; EXPANSION; EFFECTOR; THERAPY; CD4(+); RISK;

D O I：

10.1200/JCO.2011.39.8495

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose Reactivation of Epstein-Barr virus (EBV) after allogeneic stem-cell transplantation (SCT) can lead to severe life-threatening infections and trigger post-transplantation lymphoproliferative disease (PTLD). Since EBV-specific T cells could prevent PTLD, cellular immunotherapy has been a promising treatment option. However, generation of antigen-specific T-cell populations has been difficult within a short time frame. Patients and Methods To improve availability in urgent clinical conditions, we developed a rapid protocol for isolation of polyclonal EBV nuclear antigen 1 (EBNA-1) -specific T cells by using an interferon gamma (IFN-gamma) capture technique. Results We report on the use of adoptive transfer of EBNA-1-specific T cells in 10 pediatric and adult patients with EBV viremia and/or PTLD after SCT. No acute toxicity or graft-versus-host disease (GVHD) of more than grade 2 occurred as a result of adoptive T-cell transfer. In vivo expansion of transferred EBNA-1-specific T cells was observed in eight of 10 patients after a median of 16 days following adoptive transfer that was associated with clinical and virologic response in seven of them (70%). None of the responders had EBV-associated mortality. Within clinical responders, three patients were disease free by the day of last follow-up (2 to 36 months), three patients died of other infectious complications, and one patient died as a result of relapse of malignancy. EBV-related mortality was observed in two of 10 patients, and another patient had ongoing viremia without clinical symptoms at last follow-up. Conclusion Adoptive ex vivo transfer of EBNA-1-specific T cells is a feasible and well-tolerated therapeutic option, representing a fast and efficient procedure to achieve reconstitution of antiviral T-cell immunity after SCT. J Clin Oncol 31:39-48. (c) 2012 by American Society of Clinical Oncology

引用

页码：39 / 48

页数：10

共 39 条

[1] Early reconstitution of the T-cell repertoire after non-myeloablative peripheral blood stem cell transplantation is from post-thymic T-cell expansion and is unaffected by graft-versus-host disease or mixed chimaerism [J].