Adoptive T-cell therapy for B-cell acute lymphoblastic leukemia: preclinical studies

We have previously shown that leukemia-specific cytotoxic T cells (CTL) can he generated from the bone marrow of most patients with B-cell precursor a cute leukemias. If these antileukemia CTL are to be used for adoptive immun otherapy, they must have the capability to circulate, migrate through endot helium, home to the bone marrow, and, most importantly, lyse the leukemic c ells in a leukemia-permissive bone marrow microenvironment. We demonstrate here that such antileukemia T-cell lines are overwhelmingly CD8(+) and exhi bit an activated phenotype. Using a transendothelial chemotaxis assay with human endothelial cells, we observed that these T cells can be recruited an d transmigrate through vascular and bone marrow endothelium and that these transmigrated cells preserve their capacity to lyse leukemic cells, Additio nally, these antileukemia T-cell lines are capable of adhering to autologou s stromal cell layers. Finally, autologous antileukemia CTL specifically ly se leukemic cells even in the presence of autologous marrow stroma. Importa ntly, these antileukemia T-cell lines do not lyse autologous stromal cells. Thus, the capacity to generate anti-leukemia-specific T-cell lines coupled with the present findings that such cells can migrate, adhere, and functio n in the presence of the marrow microenvironment enable the development of clinical studies of adoptive transfer of antileukemia CTL for the treatment of ALL. (C) 1999 by The American Society of Hematology.