Adoptive transfer of Epstein-Barr virus-specific cytotoxic T-lymphocytes for the treatment of angiocentric lymphomas.
Angiocentric lymphoma, known as natural killer (NK)/T-cell non-Hodgkin's lymphoma, has been reported to be associated with the Epstein-Barr virus (EBV). We performed adoptive transfer of EBV-specific polyclonal T-cell lines in 3 patients with extranodal NK/T-cell lymphoma, nasal type, and evaluated the treatment for safety, immunologic reconstitution, and clinical outcomes. The tissue samples collected from the 3 patients were confirmed by polymerase chain reaction analysis to be EBV positive. In the cases of the first and second patients, EBV-transformed B-lymphoblastoid cell lines (LCLs) and T-cell lines were generated from peripheral lymphocytes of HLA-matched sibling donors. The third patient's T-cell lines were induced with autologous lymphocytes. Polyclonal T-cell infusion was carried out after high-dose radiotherapy because active relapsed disease remained in all of the patients. The first patient received 4 weekly infusions of 2 3 10(7) cells/m(2), and the second and third patients underwent treatment with 2 cycles of infusions of the same dosage. All T-cell lines showed >60% NK activity, cytotoxic T-lymphocyte (CTL) responses of >40% against autologous LCLs, and no CTL activity against patient-derived lymphoblasts. The level of cytotoxicity increased substantially in all patients after cell infusion. The 2 patients who received T-cell therapy twice had stabilized disease for more than 3 years. These safe treatments exhibited no severe inflammatory response, and no serious toxicity developed during T-cell therapy. Our findings demonstrate that adoptively transferred cells may provide reconstitution of EBV-specific CTL responses in patients with active relapsed angiocentric lymphoma. These results provide a rationale for the immunotherapy of angiocentric lymphoma.
Cho
Hyun-Il
HI
Department of Microbiology and Immunology, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seocho-Ku, Seoul, 137-701, Korea.
Hong
Young Seon
YS
Lee
Myung Ah
MA
Kim
Eun-Kyung
EK
Yoon
Sung-Hee
SH
Kim
Chun-Choo
CC
Kim
Tai-Gyu
TG
D000328:Adult; D002460:Cell Line; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000473:pathology / Q000628:therapy*; D004854:Herpesvirus 4, Human; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007694:Killer Cells, Natural / Q000473:pathology / Q000821:virology; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000628:therapy* / Q000821:virology; D008297:Male; D009669:Nose Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology / Q000637:transplantation* / Q000821:virology; D016896:Treatment Outcome