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

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.

• Authors: L Herrera, R A Farah, V A Pellegrini, D B Aquino, E S Sandler, G R Buchanan, E S Vitetta
• Journal: Leukemia (Leukemia) Vol. 14 Issue 5 Pg. 853-8 (May 2000) ISSN: 0887-6924 [Print] England
• PMID: 10803517 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD
• Antigens, CD19
• Antigens, Differentiation, B-Lymphocyte
• CD22 protein, human
• Cell Adhesion Molecules
• Immunotoxins
• Lectins
• Sialic Acid Binding Ig-like Lectin 2
• Ricin

Topics

• Adult
• Antibody Specificity
• Antigens, CD (immunology)
• Antigens, CD19 (immunology)
• Antigens, Differentiation, B-Lymphocyte (immunology)
• Apoptosis (drug effects)
• Bone Marrow Cells (pathology)
• Burkitt Lymphoma (immunology, pathology)
• Cell Adhesion Molecules
• Cell Survival (drug effects)
• Child
• Humans
• Immunotoxins (toxicity)
• Lectins
• Lymphocytes (drug effects, immunology, pathology)
• Preleukemia (immunology, pathology)
• Ricin (toxicity)
• Sialic Acid Binding Ig-like Lectin 2
• Stromal Cells (drug effects, pathology)
• Tumor Cells, Cultured