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Immunobiology

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

Leukemia volume 14, pages 853–858 (2000)Cite this article

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.

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Acknowledgements

This work was supported by Pediatric Oncology Group Novel Scientific Initiative Grant and NIH Grant T-32-CA09640. We thank Angela Mobley and Carol Walsh for excellent assistance with the FACS analysis. We also thank Darla Tate for her acquisition and transfer of patient specimens to our laboratory and the faculty and fellows in the Center for Cancer and Blood Disorders at Children's Medical Center of Dallas.

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Authors and Affiliations

  1. Cancer Immunobiology Center, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

    L Herrera, RA Farah, VA Pellegrini & ES Vitetta

  2. Department of Pediatrics, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

    L Herrera, RA Farah, ES Sandler & GR Buchanan

  3. Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

    DB Aquino

  4. The Center for Cancer and Blood Disorders, Children's Medical Center of Dallas, Dallas, TX, USA

    L Herrera, RA Farah, ES Sandler & GR Buchanan

  5. The Pediatric Oncology Group, Chicago, IL, USA

    L Herrera, ES Sandler & GR Buchanan

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Herrera, L., Farah, R., Pellegrini, V. et al. Immunotoxins against CD19 and CD22 are effective in killing precursor-B acute lymphoblastic leukemia cells in vitro. Leukemia 14, 853–858 (2000). https://doi.org/10.1038/sj.leu.2401779

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