Chimeric CD19 antibody mediates cytotoxic activity against leukemic blasts with effector cells from pediatric patients who received T-cell-depleted allografts.
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 post-transplantation treatment of minimal residual B-lineage ALLs.
Lang
Peter
P
Department of Pediatric Oncology, University Children's Hospital, University of Tübingen, Tübingen, Germany. prlang@med.uni-tuebingen.de
Barbin
Karin
K
Feuchtinger
Tobias
T
Greil
Johann
J
Peipp
Matthias
M
Zunino
Susan J
SJ
Pfeiffer
Matthias
M
Handgretinger
Rupert
R
Niethammer
Dietrich
D
Fey
Georg H
GH
D000906:Antibodies / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D018941:Antigens, CD19 / Q000276:immunology*; D002648:Child; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation; D008212:Lymphocyte Depletion; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014184:Transplantation, Homologous
D000906:Antibodies; D018941:Antigens, CD19; D011993:Recombinant Fusion Proteins