Chimeric CD19 antibody mediates cytotoxic activity against leukemic blasts with effector cells from pediatric patients who received T-cell–depleted allografts
Open Access
- 15 May 2004
- journal article
- Published by American Society of Hematology in Blood
- Vol. 103 (10), 3982-3985
- https://doi.org/10.1182/blood-2003-05-1735
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 post-transplantation treatment of minimal residual B-lineage ALLs.Keywords
This publication has 21 references indexed in Scilit:
- Transplantation of highly purified CD34+ progenitor cells from unrelated donors in pediatric leukemiaBlood, 2003
- The Absence of Fucose but Not the Presence of Galactose or Bisecting N-Acetylglucosamine of Human IgG1 Complex-type Oligosaccharides Shows the Critical Role of Enhancing Antibody-dependent Cellular CytotoxicityJournal of Biological Chemistry, 2003
- Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effectBlood, 2002
- Partially matched related donor peripheral blood progenitor cell transplantation in paediatric patients adding fludarabine and anti-lymphocyte gamma-globulinBone Marrow Transplantation, 2002
- Lack of Fucose on Human IgG1 N-Linked Oligosaccharide Improves Binding to Human FcγRIII and Antibody-dependent Cellular ToxicityJournal of Biological Chemistry, 2002
- Clinical scale isolation of T cell-depleted CD56+ donor lymphocytes in childrenBone Marrow Transplantation, 2002
- Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa geneBlood, 2002
- Rituximab therapy of patients with B-cell chronic lymphocytic leukemiaBlood, 2001
- Megadose transplantation of purified peripheral blood CD34+progenitor cells from HLA-mismatched parental donors in childrenBone Marrow Transplantation, 2001
- Human NK cells: their ligands, receptors and functionsImmunological Reviews, 1997