Optimal Elimination of Leukemic T Cells From Human Bone Marrow With T101-Ricin A-Chain Immunotoxin

• Published in: Blood Vol. 65; no. 2; pp. 289 - 297
• Main Authors: Casellas, Pierre, Canat, Xavier, Fauser, Axel A., Gros, Olivier, Laurent, Guy, Poncelet, Philippe, Jansen, Franz K.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-02-1985; The Americain Society of Hematology
• Subjects: Ammonium Chloride - pharmacology; Antibodies, Monoclonal - physiology; Biological and medical sciences; Bone Marrow - pathology; Cell Line; Cell Survival - drug effects; Clone Cells - immunology; Clone Cells - pathology; Colony-Forming Units Assay; Cytotoxins - pharmacology; Cytotoxins - toxicity; Dose-Response Relationship, Immunologic; Hematologic and hematopoietic diseases; Hematopoietic Stem Cells - drug effects; Humans; Leukemia - immunology; Leukemia - therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Ricin - pharmacology; T-Lymphocytes - immunology; Temperature; Time Factors; Human; Cell culture; Immunotoxin; Ricin; Elimination; Cytotoxicity; Malignant hemopathy; Hemopathy; Monoclonal antibody; Clonogenic assay; Autograft; Preparation; T-Lymphocyte; Bone marrow; Biomedical engineering
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V65.2.289.289

In view of bone marrow purging before autologous transplantation in T cell malignancies, an anti-human T cell immunotoxin (IT) has been prepared by coupling ricin A-chain to the monoclonal antibody T101 that binds the T1 differentiation antigen expressed by T lymphocytes as well as by T cell-derived hematologic malignancies. Using a sensitive and reliable clonogenic assay, optimal conditions were defined for the elimination of clonogenic human T leukemic cells among bone marrow cells. Maximal cytoreduction was obtained with IT at a dose of 2 μg/mL in the presence of 10 mmol/L NH4Cl. This treatment led to the reduction of more than six orders of magnitude of T101-positive clonogenic leukemic cells, with no harm to T101-negative cells. Moreover, we observed no toxicity of IT to human hematopoietic stem cells (CFU-GEMMT) derived from bone marrow of healthy volunteers. Thus, pretreatment of bone marrow samples with IT plus NH4Cl offers a safe, simple, reliable, and highly efficient means to eliminate undesirable leukemic T cells from the graft. © 1985 by Grune & Stratton, Inc.