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Treatment of SCID/human B cell precursor ALL with anti-CD19 and anti-CD22 immunotoxins

Leukemia volume 17, pages 334–338 (2003)Cite this article

Abstract

The anti-CD19 (HD37-dgRTA) and anti-CD22 (RFB4-dgRTA) immunotoxins (ITs) are murine IgG1 monoclonal antibodies (Mabs) conjugated to a deglycosylated ricin A chain (dgRTA). They are effective in killing B-lineage non-Hodgkin’s lymphoma (NHL) cells in vitro, in vivo and in adult patients with B-lineage NHL. The potential of these agents for the treatment of childhood B-precursor acute lymphoblastic leukemia (ALL) is unknown. The anti-CD19 and anti-CD22 ITs should have anti-tumor activity against childhood B-lineage ALL since both target antigens are expressed on the surface of these cells. We have previously shown that, in vitro these two ITs selectively kill leukemia cells obtained from children with leukemia. To evaluate the efficacy of our ITs in an in vivo model we injected the human pre-B ALL cell line, NALM-6-UM1, into severe combined immunodeficient (SCID) mice. We tested the ability of two ITs to prolong survival or cure mice of both early and advanced tumors. In early disease, treatment with HD37-dgRTA, RFB4-dgRTA, or Combotox (an equimolar concentration of the two ITs) significantly improved their survival. In advanced disease, treatment with RFB4-dgRTA or Combotox significantly improved survival. Overall there were 10 long-term survivors who were cured, as determined by survival beyond 150 days with no evidence of disease as determined by polymerase chain reaction (PCR) analysis.

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Acknowledgements

We thank Stacey Trammell-Garth for her secretarial assistance. We also thank Nancy Lane, Sapna Beeram, David Cummings, and Patty Nunez for technical assistance. Supported by Scott and White Memorial Hospital/Texas A&M University Health Sciences Center New Programs Initiative Grant No. 1535 and the NIH Minority Supplement to Grant No. CA77701–01.

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Authors and Affiliations

  1. Department of Pediatrics, Section of Hematology/Oncology, Scott and White Memorial Hospital/Texas A&M University Health Sciences Center, Temple, TX, USA

    L Herrera & S Yarbrough

  2. Department of Pathology UTSWMC, Dallas, TX, USA

    D B Aquino

  3. The Cancer Immunobiology Center, UTSWMC, Dallas, TX, USA

    L Herrera, V Ghetie & E S Vitetta

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  1. L Herrera
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  2. S Yarbrough
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  3. V Ghetie
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  4. D B Aquino
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  5. E S Vitetta
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Herrera, L., Yarbrough, S., Ghetie, V. et al. Treatment of SCID/human B cell precursor ALL with anti-CD19 and anti-CD22 immunotoxins. Leukemia 17, 334–338 (2003). https://doi.org/10.1038/sj.leu.2402790

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