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

Blood. 2007 Oct 1;110(7):2620-30. doi: 10.1182/blood-2006-11-059139. Epub 2007 May 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation
  • Coculture Techniques
  • Herpesvirus 4, Human / immunology*
  • Histocompatibility Antigens / immunology
  • Hodgkin Disease / immunology*
  • Hodgkin Disease / metabolism*
  • Hodgkin Disease / pathology
  • Hodgkin Disease / therapy
  • Humans
  • Immunotherapy
  • Ki-1 Antigen / immunology*
  • Ki-1 Antigen / metabolism*
  • Kinetics
  • Mice
  • Mutant Chimeric Proteins / genetics
  • Mutant Chimeric Proteins / immunology
  • Mutant Chimeric Proteins / metabolism
  • Phenotype
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / metabolism*


  • Histocompatibility Antigens
  • Ki-1 Antigen
  • Mutant Chimeric Proteins
  • Receptors, Antigen, T-Cell