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 Blood, 1 October 2007, Vol. 110, No. 7, pp. 2620-2630.
Prepublished online as a Blood First Edition Paper on May 16, 2007; DOI 10.1182/blood-2006-11-059139.

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NEOPLASIA

Epstein Barr virus–specific cytotoxic T lymphocytes expressing the anti-CD30{zeta} artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease

Barbara Savoldo1,2, Cliona M. Rooney1,3, Antonio Di Stasi1, Hinrich Abken4, Andreas Hombach4, Aaron E. Foster1, Lan Zhang1, Helen E. Heslop1,2,5, Malcolm K. Brenner1,2,5, and Gianpietro Dotti1,5

1 Center for Cell and Gene Therapy, Departments of2 Pediatrics and 3 Molecular Virology and Microbiology, Baylor College of Medicine, the Methodist Hospital and Texas Children's Hospital, Houston; 4 Tumor Genetics, University of Cologne, Cologne, Germany; 5 Department of Medicine, Baylor College of Medicine, the Methodist Hospital and Texas Children's Hospital, Houston

Adoptive transfer of Epstein Barr virus (EBV)–specific cytotoxic T-lymphocytes (EBV-CTLs) has shown that these cells persist in patients with EBV+ Hodgkin lymphoma (HD) to produce complete tumor responses. Treatment failure, however, occurs if a subpopulation of malignant cells in the tumor lacks or loses expression of EBV antigens. We have therefore determined whether we could prepare EBV-CTLs that retained the antitumor activity conferred by their native receptor while expressing a chimeric antigen receptor (CAR) specific for CD30, a molecule highly and consistently expressed on malignant Hodgkin Reed-Sternberg cells. We made a CD30CAR and were able to express it on 26% (± 11%) and 22% (± 5%) of EBV-CTLs generated from healthy donors and HD patients, respectively. These CD30CAR+ CTLs killed both autologous EBV+ cells through their native receptor and EBV–/CD30+ targets through their major histocompatibility complex (MHC)–unrestricted CAR. A subpopulation of activated T cells also express CD30, but the CD30CAR+ CTLs did not impair cellular immune responses, probably because normal T cells express lower levels of the target antigen. In a xenograft model, CD30CAR+ EBV-CTLs could be costimulated by EBV-infected cells and produce antitumor effects even against EBV–/CD30+ tumors. EBV-CTLs expressing both a native and a chimeric antigen receptor may therefore have added value for treatment of HD.


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R. F. Ambinder
Epstein-Barr Virus and Hodgkin Lymphoma
Hematology, January 1, 2007; 2007(1): 204 - 209.
[Abstract] [Full Text] [PDF]


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