title: Elimination of B-lineage leukemia and lymphoma cells from bone marrow grafts using anti-B4-blocked-ricin immunotoxin.
abstract: Bone marrow is the primary site of disease in patients with acute lymphoblastic leukemia (ALL) and is frequently involved in patients with non-Hodgkin's lymphoma (NHL). At the time of autologous bone marrow transplantation, marrow grafts from patients with leukemia and lymphoma are often still contaminated by malignant cells, even when such patients achieve complete clinical remission. In this study, we evaluated the potential of anti-B4-blocked-ricin (anti-B4-bR) immunotoxin to eliminate residual ALL and NHL cells from bone marrow. Anti-B4-bR binds to the CD19 antigen, which is B-lineage specific, and, at concentrations of 5 x 10(-9) M or greater, could eliminate more than 3 logs of CD19+ Nalm-6 or Namalwa cells in a 20-fold excess of normal irradiated bone marrow after only 5 hr of incubation. This activity was abrogated by the addition of anti-B4 but not by the presence of galactose, which is the natural ligand for native ricin. Also, when used at these high concentrations, anti-B4-bR showed little nonspecific toxicity against normal hematopoietic progenitors. In conclusion, a single short exposure to anti-B4-bR is capable of inducing high levels of depletion of CD19+ leukemia and lymphoma cells without significant nonspecific toxicity against normal marrow progenitors. Therefore, anti-B4-bR offers an interesting approach to the elimination of B-lineage malignant cells prior to autologous bone marrow transplantation.
authors.affiliation: Maisonneuve-Rosemont Hospital, Department of Medicine, Université de Montréal, Québec, Canada.
authors.forename: D C
authors.initials: DC
authors.lastname: Roy
authors.forename: C
authors.initials: C
authors.lastname: Perreault
authors.forename: R
authors.initials: R
authors.lastname: Bélanger
authors.forename: M
authors.initials: M
authors.lastname: Gyger
authors.forename: C
authors.initials: C
authors.lastname: Le Houillier
authors.forename: W A
authors.initials: WA
authors.lastname: Blättler
authors.forename: J M
authors.initials: JM
authors.lastname: Lambert
authors.forename: J
authors.initials: J
authors.lastname: Ritz
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002051:Burkitt Lymphoma / Q000276:immunology*; D006412:Hematopoietic Stem Cells; D006801:Humans; D000922:Immunotoxins; D008212:Lymphocyte Depletion / Q000379:methods*; D012276:Ricin / Q000276:immunology; D013696:Temperature; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D000922:Immunotoxins; D012276:Ricin