796. In Vivo Elimination of Human Leukaemia Cells by WT1 Specific TCR Transduced T Cells

Abstract

Previously, we have shown that to circumvent T cell tolerance to the Wilms tumor antiegn-1 (WT1), cytotoxic T lymphocytes (CTL) specific for an HLA-A2-presented peptide epitope of the WT1 have been generated from allogeneic donors, and these CTL can selectively kill immature human leukemia progenitor and stem cells in vitro. In this study we have isolated the T cell receptor (TCR) genes of an allorestricted CTL line for retroviral gene transfer into T lymphocytes obtained from both leukemia patients and healthy donors. Here we show that TCR transduced CTL kill T2 target cells coated with the WT1 peptide but not with irrelevant peptide, and these T cells also kill leukemia cells in vitro and display WT1-specific cytokine production. Intravenous injection of TCR transduced T cells into NOD/SCID mice harbouring human leukemia cells resulted in leukaemia elimination, whilst transfer of control T cells transduced with an irrelevant TCR was ineffective. These data suggest that adoptive immunotherapy with WT1-TCR gene modified patient T cells should be considered for the treatment of human leukemia.