Of mice, not men: no evidence for graft-versus-host disease in humans receiving T-cell receptor-transduced autologous T cells.

摘要

A recent article by Bendle et al. reported a high incidence of lethal graft-versus-host disease (GVHD) in mice receiving a lymphodepleting regimen followed by syngeneic cells transduced with genes encoding T-cell receptors (TCRs). The GVHD was manifested as cachexia, anemia, loss of hematopoi-etic reconstitution, pancreatitis, colitis, and death. A recent in vitro study by van Loenen et al. suggested that introduction of new TCRs into human lymphocytes could lead to the generation of mixed-TCR dimers with alloreactivity, although no in vivo data were presented. We have treated 106 patients in the Surgery Branch of the National Cancer Institute with autologous T cells transduced with seven different gammaretro-viral vectors encoding antitumor TCRs (Table 1; refs. 3 and 4 and unpublished observations) and have seen no evidence of GVHD in any patient. Each of these patients received a lympho depleting regimen of 60 mg/kg of cyclophosphamide for 2 days followed by 5 days of fludara-bine at 25 mg/m~2.