Chimeric CD19 antibody mediates cytotoxic activity against leukemic blasts with effector cells from pediatric patients who received T-cell-depleted allografts

Peter Lang, Karin Barbin, Tobias Feuchtinger, Johann Greil, Matthias Peipp, Susan J. Zunino, Matthias Pfeiffer, Rupert Handgretinger, Dietrich Niethammer, Georg H. Fey

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Relapse is a major problem after transplantation in children with acute B-lineage leukemias, and new therapies are needed to Increase graft-versus-leukemia (GvL) effects without inducing graft-versus-host disease (GvHD). Here, we studied the ability of effector cells recovered from patients after transplantation with positive-selected stem cells from alternative donors to Induce antibody-dependent cellular cytotoxicity (ADCC). For this purpose, a chimeric CD19 antibody, CD19-4G7chim, was generated. This antibody efficiently mediated ADCC against primary acute lymphoblastic leukemia (ALL) blasts by using purified natural killer (NK) cells from healthy donors or mononuclear cells from patients as effector cells. Increased lysis was obtained after stimulation of effector cells with interleukin-2 (IL-2). ADCC was not prevented by inhibitory effects mediated by HLA class I. We propose that treatment with chimeric CD19 antibodies leading to ADCC by donor-derived NK cells may become a therapeutic option for the posttransplantation treatment of minimal residual B-lineage ALLs.

Original languageEnglish (US)
Pages (from-to)3982-3985
Number of pages4
JournalBlood
Volume103
Issue number10
DOIs
StatePublished - May 15 2004
Externally publishedYes

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Pediatrics
T-cells
Allografts
T-Lymphocytes
Cytotoxicity
Antibodies
Tissue Donors
Grafts
Natural Killer Cells
Leukemia
Transplantation
Graft vs Host Disease
Therapeutics
Stem cells
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Interleukin-2
Stem Cells
Transplants
Recurrence

ASJC Scopus subject areas

  • Hematology

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Chimeric CD19 antibody mediates cytotoxic activity against leukemic blasts with effector cells from pediatric patients who received T-cell-depleted allografts. / Lang, Peter; Barbin, Karin; Feuchtinger, Tobias; Greil, Johann; Peipp, Matthias; Zunino, Susan J.; Pfeiffer, Matthias; Handgretinger, Rupert; Niethammer, Dietrich; Fey, Georg H.

In: Blood, Vol. 103, No. 10, 15.05.2004, p. 3982-3985.

Research output: Contribution to journalArticle

Lang, P, Barbin, K, Feuchtinger, T, Greil, J, Peipp, M, Zunino, SJ, Pfeiffer, M, Handgretinger, R, Niethammer, D & Fey, GH 2004, 'Chimeric CD19 antibody mediates cytotoxic activity against leukemic blasts with effector cells from pediatric patients who received T-cell-depleted allografts', Blood, vol. 103, no. 10, pp. 3982-3985. https://doi.org/10.1182/blood-2003-05-1735
Lang, Peter ; Barbin, Karin ; Feuchtinger, Tobias ; Greil, Johann ; Peipp, Matthias ; Zunino, Susan J. ; Pfeiffer, Matthias ; Handgretinger, Rupert ; Niethammer, Dietrich ; Fey, Georg H. / Chimeric CD19 antibody mediates cytotoxic activity against leukemic blasts with effector cells from pediatric patients who received T-cell-depleted allografts. In: Blood. 2004 ; Vol. 103, No. 10. pp. 3982-3985.
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