Optimal elimination of leukemic T cells from human bone marrow with T101-ricin A-chain immunotoxin.
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 micrograms/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.
D000643:Ammonium Chloride / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000502:physiology*; D001853:Bone Marrow / Q000473:pathology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D003114:Colony-Forming Units Assay; D003603:Cytotoxins / Q000494:pharmacology* / Q000633:toxicity; D004306:Dose-Response Relationship, Immunologic; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000276:immunology* / Q000628:therapy; D012276:Ricin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*; D013696:Temperature; D013997:Time Factors
D000911:Antibodies, Monoclonal; D003603:Cytotoxins; D000643:Ammonium Chloride; D012276:Ricin