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Blood, 1 December 2001, Vol. 98, No. 12, pp. 3359-3366

IMMUNOBIOLOGY

Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy

Daniela Montagna, Rita Maccario, Franco Locatelli, Vittorio Rosti, Young Yang, Peggy Farness, Antonia Moretta, Patrizia Comoli, Enrica Montini, and Antonella Vitiello

From the BMT Laboratory and BMT Units, Department of Pediatrics, Laboratory of Organ Transplantation, IRCCS Policlinico San Matteo, University of Pavia, Italy; and the Robert Wood Johnson Pharmaceutical Research Institute, San Diego, CA.

Adoptive cellular immunotherapy has proven to be a successful approach in preventing and curing cytomegalovirus infection and Epstein-Barr virus-associated lymphomas after bone marrow transplantation. Translation of this approach for preventing leukemia relapse after bone marrow transplantation might require ex vivo priming and long-term maintenance of leukemia blast-specific T cells. To accomplish this goal, procedures were optimized for the in vitro priming of naive CD8 using dendritic cells activated by CD40 ligation, interleukin-12 (IL-12), and IL-7. Using T lymphocytes and dendritic cells obtained from HLA-matched allogeneic bone marrow transplantation donors and leukemia blasts as a source of tumor antigens, anti-acute myeloid leukemia cytotoxic T lymphocytes (CTLs) were induced. In these experiments, it was found that though it is possible to induce CTLs using immature dendritic cells, IL-12, and IL-7, obtaining long-term CTLs requires the presence of CD4 T cells in the priming phase. Using this approach, long-term antileukemia CTL lines could be generated from 4 of 4 bone marrow donors. Because this procedure does not require definition of the target antigen and because it selects responding cells from a virgin T-cell repertoire, its general application is suggested in adoptive immunotherapy and in the definition of tumor rejection antigens.

© 2001 by The American Society of Hematology.
 

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