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Blood, Vol. 94 No. 10 (November 15), 1999:
pp. 3531-3540
Adoptive T-Cell Therapy for B-Cell Acute Lymphoblastic Leukemia:
Preclinical Studies
Angelo A. Cardoso,
J. Pedro Veiga,
Paolo Ghia,
Hernani M. Afonso,
W. Nicholas Haining,
Stephen E. Sallan, and
Lee M. Nadler
From the Departments of Adult Oncology and Pediatric Oncology,
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; and
the "Abel Salazar" Institute for Biomedical Sciences, Oporto
University, Oporto, Portugal.
We have previously shown that leukemia-specific cytotoxic T cells
(CTL) can be generated from the bone marrow of most patients with
B-cell precursor acute leukemias. If these antileukemia CTL are to be
used for adoptive immunotherapy, they must have the capability to
circulate, migrate through endothelium, home to the bone marrow, and,
most importantly, lyse the leukemic cells in a leukemia-permissive bone
marrow microenvironment. We demonstrate here that such antileukemia
T-cell lines are overwhelmingly CD8+ and exhibit an
activated phenotype. Using a transendothelial chemotaxis assay with
human endothelial cells, we observed that these T cells can be
recruited and transmigrate through vascular and bone marrow endothelium
and that these transmigrated cells preserve their capacity to lyse
leukemic cells. Additionally, these antileukemia T-cell lines are
capable of adhering to autologous stromal cell layers. Finally,
autologous antileukemia CTL specifically lyse leukemic cells even in
the presence of autologous marrow stroma. Importantly, 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
function in the presence of the marrow microenvironment enable the
development of clinical studies of adoptive transfer of antileukemia
CTL for the treatment of ALL.
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