Targeted α particle immunotherapy for myeloid leukemia Journal Article

Authors: Jurcic, J. G.; Larson, S. M.; Sgouros, G.; McDevitt, M. R.; Finn, R. D.; Divgi, C. R.; Ballangrud, A. M.; Hamacher, K. A.; Ma, D.; Humm, J. L.; Brechbiel, M. W.; Molinet, R.; Scheinberg, D. A.
Article Title: Targeted α particle immunotherapy for myeloid leukemia
Abstract: Unlike β particle-emitting isotopes, a emitters can selectively kill individual cancer cells with a single atomic decay. HuM195, a humanized anti-CD33 monoclonal antibody, specifically targets myeloid leukemia cells and has activity against minimal disease. When labeled with the β-emitters 131I and 90Y, HuM195 can eliminate large leukemic burdens in patients, but it produces prolonged myelosuppression requiring hematopoietic stem cell transplantation at high doses. To enhance the potency of native HuM195 yet avoid the nonspecific cytotoxicity of β-emitting constructs, the α-emitting isotope 213Bi was conjugated to HuM195. Eighteen patients with relapsed and refractory acute myelogenous leukemia or chronic myelomonocytic leukemia were treated with 10.36 to 37.0 MBq/kg 213Bi-HuM195. No significant extramedullary toxicity was seen. All 17 evaluable patients developed myelosuppression, with a median time to recovery of 22 days. Nearly all the 213Bi-HuM195 rapidly localized to and was retained in areas of leukemic involvement, including the bone marrow, liver, and spleen. Absorbed dose ratios between these sites and the whole body were 1000-fold greater than those seen with β-emitting constructs in this antigen system and patient population. Fourteen (93%) of 15 evaluable patients had reductions in circulating blasts, and 14 (78%) of 18 patients had reductions in the percentage of bone marrow blasts. This study demonstrates the safety, feasibility, and antileukemic effects of 213Bi-HuM195, and it is the first proof-of-concept for systemic targeted a particle immunotherapy in humans. © 2002 by The American Society of Hematology.
Keywords: adult; clinical article; controlled study; aged; unclassified drug; leukemia, myelomonocytic, chronic; clinical trial; drug tolerability; neutropenia; dose response; radiation dose; cancer immunotherapy; controlled clinical trial; bone marrow suppression; leukopenia; hematopoietic stem cell transplantation; cytotoxicity; drug potency; immunoreactivity; monoclonal antibody; antibodies, monoclonal; iodine 131; drug distribution; isotope labeling; thrombocyte count; cell count; bone marrow cell; radioimmunotherapy; radioisotopes; antigens, cd34; drug conjugation; drug indication; myeloid leukemia; alpha radiation; immunotoxins; bismuth; alpha particles; yttrium 90; bismuth 213; blast crisis; radiation absorption; leukemia, myelocytic, acute; monoclonal antibody hum195; human; male; female; priority journal; article; monoclonal antibody hum195 bi 213
Journal Title: Blood
Volume: 100
Issue: 4
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2002-08-15
Start Page: 1233
End Page: 1239
Language: English
PUBMED: 12149203
PROVIDER: scopus
Notes: Export Date: 14 November 2014 -- Source: Scopus