@Article{,
AUTHOR = {S. Fiorentino, M. Chopin, H. Dastot, N. Boissel, M. Reboul, L. Legrès, A. Janin, P. Aplan, F. Sigaux, Armelle Regnault},
TITLE = {Disruption of T cell regulatory pathways is necessary for immunotherapeutic cure of T cell acute lymphoblastic leukemia in mice},
JOURNAL = {European Cytokine Network},
VOLUME = {16},
YEAR = {2005},
NUMBER = {4},
PAGES = {300--308},
URL = {http://www.techscience.com/ECN/v16n4/66208},
ISSN = {1952-4005},
ABSTRACT = {Acute lymphoblastic leukemia (ALL) is the most common cancer in children. In recent years, the
outcome has been globally improved by current therapies, but it remains poor in patients with high, persistent
residual disease following the first course of chemotherapy, prompting evaluation of the possible beneficial effects
of immunotherapy protocols. In this study, we hypothesized that the disruption of two immunoregulatory
pathways controlling the auto-reactive T cell response might synergize with dendritic cell-based immunotherapy
of the disease, which is considered to be poorly immunogenic. In this study, we used TAL1xLMO1 leukemia cells
adoptively transferred in mice, to generate murine leukemia with poorly immunogenic cells as a model for human
T-ALL. Subsequently, these animals were treated with several different immunotherapeutic protocols. We
compared the efficiency of a classical, dendritic cell-based immunotherapy (injection of dendritic cells loaded with
tumor-derived antigenic products), to a combined treatment associating injection of antigen-loaded dendritic cells
and disruption of the two immunoregulatory pathways: CD25+ suppressive T cells and cytotoxic T lymphocyteassociated
antigens (CTLA-4). We show that this combined treatment resulted in cure, concomitantly with in vivo
generation of immune memory, and TNF-alpha secretion. This study demonstrates that the disruption of these two
immunoregulatory pathways synergized with immunostimulation by dendritic cells loaded with tumor-derived
antigens, and paves the way for the testing of this combination in clinical trials.},
DOI = {}
}