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

L. Herrera, S. Yarbrough, V. Ghetie, D. B. Aquino, E. S. Vitetta

Research output: Contribution to journalArticle

50 Scopus citations

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 antitumor 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.

Original languageEnglish (US)
Pages (from-to)334-338
Number of pages5
JournalLeukemia
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2003

Keywords

  • Childhood leukemia
  • Immunotherapy
  • Monoclonal antibodies
  • NALM-6-UM1

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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