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

Adoptive cellular immunotherapy has proven to be a successful approach in p reventing and curing cytomegalovirus infection and Epstein-Barr virus-assoc iated lymphomas after bone marrow transplantation. Translation of this appr oach for preventing leukemia relapse after bone marrow transplantation migh t require ex vivo priming and long-term maintenance of leukemia blast-speci fic 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 an d leukemia blasts as a source of tumor antigens, anti-acute myeloid leukemi a cytotoxic T lymphocytes (CTLs) were induced. In these experiments, it was found that though it is possible to induce CTLs using immature dendritic c ells, IL-12, and IL-7, obtaining long-term CTLs requires the presence of CD 4 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 appli cation is suggested in adoptive immunotherapy and in the definition of tumo r rejection antigens. (Blood. 2001;98: 3359-3366) (C) 2001 by The American Society of Hematology.