Abstract
Monoclonal antibodies (Mabs) conjugated to toxins or their subunits (immunotoxins or ITs) are undergoing clinical testing in adults with a variety of malignancies. The potential impact of this form of therapy in pediatric precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) has yet to be determined. Mabs directed against the cell surface antigens, CD19 and CD22 conjugated to deglycosylated ricin A chain (dgRTA) have been tested in patients with non-Hodgkin's lymphoma (NHL), but not in patients with pre-B ALL. Because of the encouraging performance of these ITs in phase I trials, we evaluated the specific cytotoxicity of anti-CD19 (HD37-dgRTA) and anti-CD22 (RFB4-dgRTA) ITs or their combination (Combotox) on patient-derived pre-B ALL cells maintained in vitro on a stromal feeder layer. After 48 h in culture, cytotoxicity to tumor cells was determined by flow cytometry using propidium iodide (PI) and fluorescein isothiocyanate (FITC)-conjugated anti-CD10, 19, and 22. Both RFB4-dgRTA and HD37-dgRTA induced a statistically significant reduction in the number of viable leukemic cells, and Combotox was even more effective. Our results demonstrate that these ITs are specifically cytotoxic to primary pre-B ALL cells and that they should be further evaluated for the therapy of B-lineage ALL.
Original language | English (US) |
---|---|
Pages (from-to) | 853-858 |
Number of pages | 6 |
Journal | Leukemia |
Volume | 14 |
Issue number | 5 |
DOIs | |
State | Published - 2000 |
Keywords
- Childhood leukemia
- Immunotherapy
- Immunotoxins
- Monoclonal antibodies
- Pre-B ALL
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research