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, Antonella Vitiello

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3359-3366
Number of pages8
JournalBlood
Volume98
Issue number12
DOIs
Publication statusPublished - Dec 1 2001

Fingerprint

Adoptive Immunotherapy
T-cells
Cytotoxic T-Lymphocytes
Bone Marrow Transplantation
Dendritic Cells
T-Lymphocytes
Interleukin-7
Leukemia
Neoplasm Antigens
Interleukin-12
Bone
Homologous Transplantation
Cytomegalovirus Infections
Human Herpesvirus 4
Acute Myeloid Leukemia
Ligation
Lymphoma
Bone Marrow
Antigens
Recurrence

ASJC Scopus subject areas

  • Hematology

Cite this

Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy. / Montagna, Daniela; Maccario, Rita; Locatelli, Franco; Rosti, Vittorio; Yang, Young; Farness, Peggy; Moretta, Antonia; Comoli, Patrizia; Montini, Enrica; Vitiello, Antonella.

In: Blood, Vol. 98, No. 12, 01.12.2001, p. 3359-3366.

Research output: Contribution to journalArticle

@article{87eba23d10db49e5955e32d8b033a8b4,
title = "Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy",
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.",
author = "Daniela Montagna and Rita Maccario and Franco Locatelli and Vittorio Rosti and Young Yang and Peggy Farness and Antonia Moretta and Patrizia Comoli and Enrica Montini and Antonella Vitiello",
year = "2001",
month = "12",
day = "1",
doi = "10.1182/blood.V98.12.3359",
language = "English",
volume = "98",
pages = "3359--3366",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "12",

}

TY - JOUR

T1 - Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy

AU - Montagna, Daniela

AU - Maccario, Rita

AU - Locatelli, Franco

AU - Rosti, Vittorio

AU - Yang, Young

AU - Farness, Peggy

AU - Moretta, Antonia

AU - Comoli, Patrizia

AU - Montini, Enrica

AU - Vitiello, Antonella

PY - 2001/12/1

Y1 - 2001/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035760880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035760880&partnerID=8YFLogxK

U2 - 10.1182/blood.V98.12.3359

DO - 10.1182/blood.V98.12.3359

M3 - Article

C2 - 11719375

AN - SCOPUS:0035760880

VL - 98

SP - 3359

EP - 3366

JO - Blood

JF - Blood

SN - 0006-4971

IS - 12

ER -