Killing of non-Hodgkin lymphoma cells by autologous CD19 engineered T cells

Br J Haematol. 2005 May;129(3):322-32. doi: 10.1111/j.1365-2141.2005.05456.x.


Adoptive immunotherapy with tumour-specific T cells is an emerging technology that may be applicable to a broad range of cancers. However, tumours can avoid T cell-mediated attack through multiple mechanisms including downregulation of major histocompatability complex (MHC). Consequently, engineering T cells to target intact protein antigen directly, thus bypassing the need for MHC presentation, can facilitate T cell targeting of tumour cells. Peripheral blood lymphocytes from nine of nine patients with non-Hodgkin lymphoma (NHL) were successfully gene-modified to express a receptor consisting of a CD19 single chain variable fragment (scFv) fused to the T cell CD3zeta signalling molecule. These T cells were functionally active against the CD19(+) Raji Burkitt's lymphoma cell line. Importantly, engineered T cells from seven of nine NHL patients efficiently lysed autologous lymph node tumour biopsy cells. There was a clear correlation between levels of CD19 expression on the tumour and effective killing by the engineered T cells. For two patients with a low or absent CD19(+) cells within the biopsy, no significant killing was observed. These results demonstrate that patients with CD19(+) NHL would be suitable candidates for this form of therapy in the setting of a phase I clinical trial.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD19 / analysis*
  • Biopsy
  • CD3 Complex / immunology
  • Cytotoxicity, Immunologic
  • Female
  • Genetic Vectors
  • Humans
  • Immunotherapy, Adoptive / methods
  • Interferon-gamma / biosynthesis
  • Lymphocyte Activation
  • Lymphocyte Transfusion / methods*
  • Lymphoma, Non-Hodgkin / immunology
  • Lymphoma, Non-Hodgkin / pathology*
  • Male
  • Middle Aged
  • Retroviridae / genetics
  • T-Lymphocyte Subsets / immunology*
  • Transduction, Genetic
  • Tumor Cells, Cultured


  • Antigens, CD19
  • CD3 Complex
  • CD3 antigen, zeta chain
  • Interferon-gamma