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Epstein-Barr Virus (EBV)-Specific Cytotoxic T Lymphocytes for the
Treatment of Patients With EBV-Positive Relapsed Hodgkin's Disease
Marie A. Roskrow,
Nobuhiro Suzuki,
Yan-jun Gan,
John W. Sixbey,
Catherine Y.C. Ng,
Sarah Kimbrough,
Melissa Hudson,
Malcolm K. Brenner,
Helen E. Heslop, and
Cliona M. Rooney
From the Departments of Virology and Molecular Biology, Infectious
Diseases, and Hematology/Oncology, and Division of Bone Marrow
Transplantation, St Jude Children's Research Hospital, Memphis, TN;
and the Department of Pediatrics and Pathology, University of Tennessee
College of Medicine, Memphis, TN.
Adoptive transfer of Epstein-Barr virus (EBV)-specific cytotoxic T
lymphocytes (CTLs) is effective prophylaxis and treatment of
EBV-positive immunoblastic lymphoma in immunocompromised patients. In
50% of patients with Hodgkin's disease, the tumor cells are EBV
antigen-positive and may therefore also be suitable targets for
treatment with virus-specific CTLs. However, Hodgkin's disease may
produce several inhibitory effects on immune induction and effector
function in vivo, which may preclude the generation or effector
function of CTLs reactive against EBV viral proteins, including those
expressed by the tumor cells. We have investigated whether EBV-specific
CTLs could be generated ex vivo from 13 patients with Hodgkin's
disease: nine with active relapsed disease and four who were in
clinical remission after a first or subsequent relapse. CTL lines were
successfully generated from nine of 13 patients (five active disease,
four remission). Although these lines had an abnormal pattern of
expansion comparable to EBV-specific CTLs generated from normal donors,
their phenotype was normal except for reduced expression of the zeta
chain of the T-cell receptor (TCR). Their cytotoxicity was also
compared to EBV-specific lines generated from normal donors and
included activity against LMP2a, one of the three weakly immunogenic
viral antigens expressed by Hodgkin's tumor cells. To assess the
activity of the CTLs in vivo, they were gene-marked and infused into
three patients with multiply relapsed disease. The CTLs persisted for
more than 13 weeks postinfusion and retained their potent antiviral
effects in vivo, thereby enhancing the patient immune response to EBV. This approach may therefore have value in the treatment of EBV-positive Hodgkin's disease.
Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 2925-2934
© 1998 by The American Society of Hematology.
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