Bone marrow purging studies in acute myelogenous leukemia using the recombinant anti-CD33 immunotoxin HuM195/rGel.
This study was designed to determine the effect of immunotoxin HuM195/rGel on normal human bone marrow before clinical purging. HuM195/rGel is composed of the recombinant plant toxin gelonin (rGel) chemically coupled to the anti-CD33 human chimeric antibody HuM195. The CD33 antigen is of significant interest as a target for therapy of acute myelogenous leukemia because it is present in leukemic blasts of most patients but absent in the earliest progenitor bone marrow cells. HuM195/rGel was optimally cytotoxic to acute myelogenous leukemia HL60 cells with 24 hours of exposure. We developed an in vivo purging model by mixing mobilized peripheral blood progenitor cells with HL60 cells to simulate a remission in bone marrow. Cells were treated with 10 nmol/L of HuM195/rGel either with or without exposure to freeze/thaw procedure, which has been reported to act synergistically with HuM195/rGel to produce cytotoxic effect. When clonogenic cell recovery rates were determined, HuM195/rGel alone did not affect normal peripheral blood progenitor cells, whereas HuM195/rGel plus freeze/thaw provided 2 logs of tumor cell elimination in our purging model. We also observed similar results under conditions used in the transplantation setting. We concluded that for acute myelogenous leukemia blasts expressing CD33, HuM195/rGel could be useful as a purging reagent for autologous transplantation.
Duzkale
Hatice
H
Department of Special Medical Education Programs and Adult Leukemia Research Program, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Pagliaro
Lance C
LC
Rosenblum
Michael G
MG
Varan
Ali
A
Liu
Baoshun
B
Reuben
James
J
Wierda
William G
WG
Korbling
Martin
M
McMannis
John D
JD
Glassman
Armand B
AB
Scheinberg
David A
DA
Freireich
Emil J
EJ
D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology; D016465:Bone Marrow Purging; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells / Q000187:drug effects* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007951:Leukemia, Myeloid / Q000276:immunology / Q000628:therapy*; D008954:Models, Biological; D010940:Plant Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D054789:Ribosome Inactivating Proteins, Type 1; D063268:Sialic Acid Binding Ig-like Lectin 3; D014410:Tumor Stem Cell Assay
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; C483505:HuM195-gelonin; D000922:Immunotoxins; D010940:Plant Proteins; D011994:Recombinant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D063268:Sialic Acid Binding Ig-like Lectin 3