Immunotoxins against CD19 and CD22 are effective in killing precursor-B acute lymphoblastic leukemia cells in vitro

L. Herrera, R. A. Farah, V. A. Pellegrini, D. B. Aquino, E. S. Sandler, G. R. Buchanan, E. S. Vitetta

Research output: Contribution to journalArticle

60 Scopus citations

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 languageEnglish (US)
Pages (from-to)853-858
Number of pages6
JournalLeukemia
Volume14
Issue number5
DOIs
StatePublished - Jan 1 2000

Keywords

  • Childhood leukemia
  • Immunotherapy
  • Immunotoxins
  • Monoclonal antibodies
  • Pre-B ALL

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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