1. ¹Department of Pediatrics, Section of Hematology/Oncology, Scott and White Memorial Hospital/Texas A&M University Health Sciences Center, Temple, TX, USA
2. ²Department of Pathology UTSWMC, Dallas, TX, USA
3. ³The Cancer Immunobiology Center, UTSWMC, Dallas, TX, USA

Correspondence: L Herrera, Cancer Immunotherapy Laboratory/ Medical Research Bldg, Scott and White Memorial Hospital/Texas A&M University Health Sciences Center, 2401 South 31st Street, Temple, Texas 76508, USA; Fax: 254–742–7191

Received 21 February 2002; Accepted 11 September 2002.

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.