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.
Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy / Montagna, D.; Maccario, R.; Locatelli, F.; Rosti, V.; Yang, Y.; Farness, P.; Moretta, A.; Comoli, P.; Montini, E.; Vitiello, A.. - In: BLOOD. - ISSN 0006-4971. - 98:12(2001), pp. 3359-3366. [10.1182/blood.V98.12.3359]
Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy
Locatelli F.;
2001
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.