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Targeted alpha particle immunotherapy for myeloid leukemia
Joseph G Jurcic1, Steven M Larson, George Sgouros
1Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, New York, NY 10021, USA. jurcicj@mskcc.org
Blood
|August 1, 2002
Summary
Targeted alpha therapy using Bismuth-213 conjugated to HuM195 (213Bi-HuM195) shows promise for treating acute myelogenous leukemia. This novel approach effectively reduced leukemia cells with manageable myelosuppression, demonstrating a new avenue for cancer treatment.
Area of Science:
- Oncology
- Radiopharmaceutical Therapy
- Immunotherapy
Background:
- Alpha emitters offer precise cancer cell targeting, unlike beta emitters.
- HuM195, an anti-CD33 antibody, targets myeloid leukemia cells.
- Previous HuM195 conjugates with beta emitters caused significant myelosuppression.
Purpose of the Study:
- To evaluate the safety and efficacy of (213)Bi-HuM195 in patients with relapsed/refractory leukemia.
- To assess the therapeutic potential of targeted alpha particle immunotherapy.
Main Methods:
- Eighteen patients with acute myelogenous leukemia or chronic myelomonocytic leukemia received (213)Bi-HuM195.
- Dosage ranged from 10.36 to 37.0 MBq/kg.
- Patient response and toxicity were closely monitored.
Main Results:
- No significant extramedullary toxicity was observed.
- Myelosuppression occurred in 17 evaluable patients, with a median recovery time of 22 days.
- (213)Bi-HuM195 localized effectively to leukemic sites, achieving higher absorbed dose ratios compared to beta emitters.
- Significant reductions in circulating and bone marrow blasts were observed in most patients.
Conclusions:
- Systemic targeted alpha particle immunotherapy with (213)Bi-HuM195 is safe and feasible.
- This therapy demonstrated significant antileukemic effects in humans.
- This study provides the first proof-of-concept for systemic alpha particle immunotherapy.