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Blood. 2007 Oct 1;110(7):2620-30. Epub 2007 May 16.

Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30zeta artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease.

Author information

1
Center for Cell and Gene Therapy, Baylor College of Medicine, the Methodist Hospital and Texas Children's Hospital, Houston, TX 77030, USA. bsavoldo@bcm.tmc.edu

Abstract

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.

PMID:
17507664
PMCID:
PMC1988944
DOI:
10.1182/blood-2006-11-059139
[Indexed for MEDLINE]
Free PMC Article
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