Graft Versus Leukemia Response Without Graft-versus-host Disease Elicited By Adoptively Transferred Multivirus-specific T-cells

被引:25
作者
Melenhorst, Jan J. [1 ,6 ]
Castillo, Paul [2 ,3 ]
Hanley, Patrick J. [4 ,5 ]
Keller, Michael D. [4 ,5 ]
Krance, Robert A. [2 ,3 ]
Margolin, Judith [2 ,3 ]
Leen, Ann M. [2 ,3 ]
Heslop, Helen E. [2 ,3 ]
Barrett, A. John [1 ]
Rooney, Cliona M. [2 ,3 ]
Bollard, Catherine M. [2 ,3 ,4 ,5 ]
机构
[1] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA
[2] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA
[3] Houston Methodist Hosp, Houston, TX USA
[4] Childrens Natl Hlth Syst, Program Cell Enhancement & Technol Immunotherapy, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC USA
[5] Childrens Natl Hlth Syst, Ctr Canc & Immunol Res, Washington, DC USA
[6] Univ Penn, Translat Res Program, Perelman Sch Med, Philadelphia, PA 19104 USA
关键词
ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW TRANSPLANT; EPSTEIN-BARR-VIRUS; LYMPHOPROLIFERATIVE DISEASE; PROPHYLACTIC INFUSION; HUMAN CYTOMEGALOVIRUS; CORD BLOOD; EBV; DONOR; RECIPIENTS;
D O I
10.1038/mt.2014.192
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
A 12-year-old boy with refractory acute lymphoblastic leukemia received a haploidentical transplant from his mother. As prophylaxis for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and adenovirus, he received ex vivo expanded virus-specific donor T cells 3.5 months after transplant. Four weeks later leukemic blasts bearing the E2A deletion, identified by fluorescent in situ hybridization (FISH), appeared transiently in the blood followed by a FISH-negative hematological remission, which was sustained until a testicular relapse 3.5 months later. Clearance of the circulating leukemic cells coincided with a marked increase in circulating virus-specific T cells. The virus-specific cytotoxic T-cell (CTL) line showed strong polyfunctional reactivity with the patient's leukemic cells but not phytohemagglutinin (PHA) blasts, suggesting that virus-specific CTL lines may have clinically significant antileukemia activity.
引用
收藏
页码:179 / 183
页数:5
相关论文
共 36 条
[1]   Allo-HLA reactivity of virus-specific memory T cells is common [J].
Amir, Avital L. ;
D'Orsogna, Lloyd J. A. ;
Roelen, Dave L. ;
van Loenen, Marleen M. ;
Hagedoorn, Renate S. ;
de Boer, Renate ;
van der Hoorn, Menno A. W. G. ;
Kester, Michel G. D. ;
Doxiadis, Ilias I. N. ;
Falkenburg, J. H. Frederik ;
Claas, Frans H. J. ;
Heemskerk, Mirjam H. M. .
BLOOD, 2010, 115 (15) :3146-3157
[2]   Donor and Recipient CMV Serostatus and Outcome of Pediatric Allogeneic HSCT for Acute Leukemia in the Era of CMV-Preemptive Therapy [J].
Behrendt, Carolyn E. ;
Rosenthal, Joseph ;
Bolotin, Ellen ;
Nakamura, Ryotaro ;
Zaia, John ;
Forman, Stephen J. .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2009, 15 (01) :54-60
[3]   Host MHC class II+ antigen-presentirig cells and CD4 cells are required for CD8-mediated graft-versus-leukemia responses following delayed donor leukocyte infusions [J].
Chakraverty, Ronjon ;
Eom, Hyeon-Seok ;
Sachs, Jessica ;
Buchli, Jennifer ;
Cotter, Pete ;
Hsu, Richard ;
Zhao, Guiling ;
Sykes, Megan .
BLOOD, 2006, 108 (06) :2106-2113
[4]   Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia [J].
Chessells, JM ;
Veys, P ;
Kempski, H ;
Henley, P ;
Leiper, A ;
Webb, D ;
Hann, IM .
BRITISH JOURNAL OF HAEMATOLOGY, 2003, 123 (03) :396-405
[5]   Phenotypic and functional heterogeneity of human NK cells developing after umbilical cord blood transplantation: a role for human cytomegalovirus? [J].
Della Chiesa, Mariella ;
Falco, Michela ;
Podesta, Marina ;
Locatelli, Franco ;
Moretta, Lorenzo ;
Frassoni, Francesco ;
Moretta, Alessandro .
BLOOD, 2012, 119 (02) :399-410
[6]   Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation [J].
Doubrovina, Ekaterina ;
Oflaz-Sozmen, Banu ;
Prockop, Susan E. ;
Kernan, Nancy A. ;
Abramson, Sara ;
Teruya-Feldstein, Julie ;
Hedvat, Cyrus ;
Chou, Joanne F. ;
Heller, Glenn ;
Barker, Juliet N. ;
Boulad, Farid ;
Castro-Malaspina, Hugo ;
George, Diane ;
Jakubowski, Ann ;
Koehne, Guenther ;
Papadopoulos, Esperanza B. ;
Scaradavou, Andromachi ;
Small, Trudy N. ;
Khalaf, Ramzi ;
Young, James W. ;
O'Reilly, Richard J. .
BLOOD, 2012, 119 (11) :2644-2656
[7]   Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients [J].
Elmaagacli, Ahmet H. ;
Steckel, Nina K. ;
Koldehoff, Michael ;
Hegerfeldt, Yael ;
Trenschel, Rudolf ;
Ditschkowski, Markus ;
Christoph, Sandra ;
Gromke, Tanja ;
Kordelas, Lambros ;
Ottinger, Hellmut D. ;
Ross, Rudolf S. ;
Horn, Peter A. ;
Schnittger, Susanne ;
Beelen, Dietrich W. .
BLOOD, 2011, 118 (05) :1402-1412
[8]  
Fletcher JM, 1998, J IMMUNOL, V161, P2365
[9]   Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function [J].
Foley, Bree ;
Cooley, Sarah ;
Verneris, Michael R. ;
Pitt, Michelle ;
Curtsinger, Julie ;
Luo, Xianghua ;
Lopez-Verges, Sandra ;
Lanier, Lewis L. ;
Weisdorf, Daniel ;
Miller, Jeffrey S. .
BLOOD, 2012, 119 (11) :2665-2674
[10]   Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant [J].
Gerdemann, Ulrike ;
Katari, Usha L. ;
Papadopoulou, Anastasia ;
Keirnan, Jacqueline M. ;
Craddock, John A. ;
Liu, Hao ;
Martinez, Caridad A. ;
Kennedy-Nasser, Alana ;
Leung, Kathryn S. ;
Gottschalk, Stephen M. ;
Krance, Robert A. ;
Brenner, Malcolm K. ;
Rooney, Cliona M. ;
Heslop, Helen E. ;
Leen, Ann M. .
MOLECULAR THERAPY, 2013, 21 (11) :2113-2121