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Killing of non‐Hodgkin lymphoma cells by autologous CD19 engineered T cells
Author(s) -
Cheadle Eleanor J.,
Gilham David E.,
Thistlethwaite Fiona C.,
Radford John A.,
Hawkins Robert E.
Publication year - 2005
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2005.05456.x
Subject(s) - cd19 , lymphoma , medicine , immunology , cancer research , t cell , lymph node , immunotherapy , antigen , immune system
Summary 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 CD3 ζ 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.