Bone marrow purging studies in acute myelogenous leukemia using the recombinant anti-CD33 immunotoxin HuM195/rGel Journal Article
| Authors: | Duzkale, H.; Pagliaro, L. C.; Rosenblum, M. G.; Varan, A.; Liu, B.; Reuben, J.; Wierda, W. G.; Korbling, M.; McMannis, J. D.; Glassman, A. B.; Scheinberg, D. A.; Freireich, E. J. |
| Article Title: | Bone marrow purging studies in acute myelogenous leukemia using the recombinant anti-CD33 immunotoxin HuM195/rGel |
| Abstract: | 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. © 2003 American Society for Blood and Marrow Transplantation. |
| Keywords: | controlled study; acute granulocytic leukemia; human cell; drug efficacy; drug safety; drug targeting; antigen expression; bone marrow cells; biological model; models, biological; in vivo study; cytotoxicity; dose-response relationship, drug; simulation; antibodies, monoclonal; thawing; drug mechanism; peripheral blood stem cell; leukemia, myeloid; recombinant proteins; tumor cell; stem cell mobilization; hematopoietic stem cells; bone marrow cell; antigens, cd; colony-forming units assay; drug exposure; reagent; acute disease; cd33 antigen; clonogenesis; leukemia remission; antigens, differentiation, myelomonocytic; blast cell; autologous bone marrow transplantation; bone marrow purging; chimeric antibody; immunotoxin; immunotoxins; freezing; tumor stem cell assay; monoclonal antibody m 195; hl-60 cells; cell strain hl 60; plant proteins; drug mixture; gelonin; humans; human; article; acute myelogenous leukemia (aml); anti-cd33 immunotoxin; hum195/rgel |
| Journal Title: | Biology of Blood and Marrow Transplantation |
| Volume: | 9 |
| Issue: | 6 |
| ISSN: | 1083-8791 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2003-06-01 |
| Start Page: | 364 |
| End Page: | 372 |
| Language: | English |
| DOI: | 10.1016/s1083-8791(03)00129-0 |
| PUBMED: | 12813444 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
