Generation of alloreactive anti-leukemic cytotoxic T lymphocytes with attenuated GVHD properties from haploidentical parents in childhood acute lymphoblastic leukemia

I. Jurickova, E. K. Waller, Andrew M Yeager, M. W. Boyer

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We sought to generate alloreactive leukemia-reactive cytotoxic T lymphocytes from haploidentical parents by culture of peripheral blood mononuclear cells in vitro with irradiated leukemic blasts and IL-2 from children with ALL. After 21 days in culture the mean cytotoxicity of haploidentical lymphocytes against ALL blasts was 38% (n = 11). Cultured parental CTL were not leukemia specific but alloreactive as evidenced by equivalent cytotoxicity against stimulating ALL blasts and ConA-stimulated blasts from the other parent. The cultures yielded primarily CD8+ T cells (59%). Irradiation of CTL limited proliferation by 96% but had no short-term effects on leukemia reactive cytotoxicity, suggesting a means to limit GVHD potential in vivo. One patient was treated for relapse of ALL post-haploidentical transplant with CTL generated from the original donor. A total of nine infusions were given: the first three were irradiated, while the last six were not due to disease progression. The patient experienced clearance of peripheral blasts, and despite concomitant infusion of IL-2 with the last three CTL infusions, did not experience immediate GVHD reactions. We conclude that ALL blasts are sufficiently immunostimulatory to generate in vitro CTL with provision of exogenous IL-2, and that these CTL could exert an anti-leukemia effect in vivo.

Original languageEnglish (US)
Pages (from-to)687-697
Number of pages11
JournalBone Marrow Transplantation
Volume30
Issue number10
DOIs
StatePublished - Nov 2002
Externally publishedYes

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Cytotoxic T-Lymphocytes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Parents
Interleukin-2
Disease Progression
Blood Cells
Tissue Donors
Lymphocytes
T-Lymphocytes
Transplants
Recurrence
In Vitro Techniques

Keywords

  • Acute lymphoblastic leukemia
  • Cellular immunotherapy
  • Cytotoxic T lymphocytes (CTL)
  • Graft-versus-leukemia (GVL)
  • Lymphokines

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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title = "Generation of alloreactive anti-leukemic cytotoxic T lymphocytes with attenuated GVHD properties from haploidentical parents in childhood acute lymphoblastic leukemia",
abstract = "We sought to generate alloreactive leukemia-reactive cytotoxic T lymphocytes from haploidentical parents by culture of peripheral blood mononuclear cells in vitro with irradiated leukemic blasts and IL-2 from children with ALL. After 21 days in culture the mean cytotoxicity of haploidentical lymphocytes against ALL blasts was 38{\%} (n = 11). Cultured parental CTL were not leukemia specific but alloreactive as evidenced by equivalent cytotoxicity against stimulating ALL blasts and ConA-stimulated blasts from the other parent. The cultures yielded primarily CD8+ T cells (59{\%}). Irradiation of CTL limited proliferation by 96{\%} but had no short-term effects on leukemia reactive cytotoxicity, suggesting a means to limit GVHD potential in vivo. One patient was treated for relapse of ALL post-haploidentical transplant with CTL generated from the original donor. A total of nine infusions were given: the first three were irradiated, while the last six were not due to disease progression. The patient experienced clearance of peripheral blasts, and despite concomitant infusion of IL-2 with the last three CTL infusions, did not experience immediate GVHD reactions. We conclude that ALL blasts are sufficiently immunostimulatory to generate in vitro CTL with provision of exogenous IL-2, and that these CTL could exert an anti-leukemia effect in vivo.",
keywords = "Acute lymphoblastic leukemia, Cellular immunotherapy, Cytotoxic T lymphocytes (CTL), Graft-versus-leukemia (GVL), Lymphokines",
author = "I. Jurickova and Waller, {E. K.} and Yeager, {Andrew M} and Boyer, {M. W.}",
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T1 - Generation of alloreactive anti-leukemic cytotoxic T lymphocytes with attenuated GVHD properties from haploidentical parents in childhood acute lymphoblastic leukemia

AU - Jurickova, I.

AU - Waller, E. K.

AU - Yeager, Andrew M

AU - Boyer, M. W.

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N2 - We sought to generate alloreactive leukemia-reactive cytotoxic T lymphocytes from haploidentical parents by culture of peripheral blood mononuclear cells in vitro with irradiated leukemic blasts and IL-2 from children with ALL. After 21 days in culture the mean cytotoxicity of haploidentical lymphocytes against ALL blasts was 38% (n = 11). Cultured parental CTL were not leukemia specific but alloreactive as evidenced by equivalent cytotoxicity against stimulating ALL blasts and ConA-stimulated blasts from the other parent. The cultures yielded primarily CD8+ T cells (59%). Irradiation of CTL limited proliferation by 96% but had no short-term effects on leukemia reactive cytotoxicity, suggesting a means to limit GVHD potential in vivo. One patient was treated for relapse of ALL post-haploidentical transplant with CTL generated from the original donor. A total of nine infusions were given: the first three were irradiated, while the last six were not due to disease progression. The patient experienced clearance of peripheral blasts, and despite concomitant infusion of IL-2 with the last three CTL infusions, did not experience immediate GVHD reactions. We conclude that ALL blasts are sufficiently immunostimulatory to generate in vitro CTL with provision of exogenous IL-2, and that these CTL could exert an anti-leukemia effect in vivo.

AB - We sought to generate alloreactive leukemia-reactive cytotoxic T lymphocytes from haploidentical parents by culture of peripheral blood mononuclear cells in vitro with irradiated leukemic blasts and IL-2 from children with ALL. After 21 days in culture the mean cytotoxicity of haploidentical lymphocytes against ALL blasts was 38% (n = 11). Cultured parental CTL were not leukemia specific but alloreactive as evidenced by equivalent cytotoxicity against stimulating ALL blasts and ConA-stimulated blasts from the other parent. The cultures yielded primarily CD8+ T cells (59%). Irradiation of CTL limited proliferation by 96% but had no short-term effects on leukemia reactive cytotoxicity, suggesting a means to limit GVHD potential in vivo. One patient was treated for relapse of ALL post-haploidentical transplant with CTL generated from the original donor. A total of nine infusions were given: the first three were irradiated, while the last six were not due to disease progression. The patient experienced clearance of peripheral blasts, and despite concomitant infusion of IL-2 with the last three CTL infusions, did not experience immediate GVHD reactions. We conclude that ALL blasts are sufficiently immunostimulatory to generate in vitro CTL with provision of exogenous IL-2, and that these CTL could exert an anti-leukemia effect in vivo.

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KW - Cellular immunotherapy

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KW - Graft-versus-leukemia (GVL)

KW - Lymphokines

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