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.