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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.
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