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Treatment of SCID/human B cell precursor ALL with anti-CD19 and anti-CD22 immunotoxins.
Leukemia. 2003 Feb; 17(2):334-8.L

Abstract

The anti-CD19 (HD37-dgRTA) and anti-CD22 (RFB4-dgRTA) immunotoxins (ITs) are murine IgG(1) 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.

Authors+Show Affiliations

Department of Pediatrics, Section of Hematology/Oncology, Scott and White Memorial Hospital/Texas A&M University Health Sciences Center, Temple, TX 76508, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12592332

Citation

Herrera, L, et al. "Treatment of SCID/human B Cell Precursor ALL With anti-CD19 and anti-CD22 Immunotoxins." Leukemia, vol. 17, no. 2, 2003, pp. 334-8.
Herrera L, Yarbrough S, Ghetie V, et al. Treatment of SCID/human B cell precursor ALL with anti-CD19 and anti-CD22 immunotoxins. Leukemia. 2003;17(2):334-8.
Herrera, L., Yarbrough, S., Ghetie, V., Aquino, D. B., & Vitetta, E. S. (2003). Treatment of SCID/human B cell precursor ALL with anti-CD19 and anti-CD22 immunotoxins. Leukemia, 17(2), 334-8.
Herrera L, et al. Treatment of SCID/human B Cell Precursor ALL With anti-CD19 and anti-CD22 Immunotoxins. Leukemia. 2003;17(2):334-8. PubMed PMID: 12592332.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treatment of SCID/human B cell precursor ALL with anti-CD19 and anti-CD22 immunotoxins. AU - Herrera,L, AU - Yarbrough,S, AU - Ghetie,V, AU - Aquino,D B, AU - Vitetta,E S, PY - 2002/02/21/received PY - 2002/09/11/accepted PY - 2003/2/20/pubmed PY - 2003/4/12/medline PY - 2003/2/20/entrez SP - 334 EP - 8 JF - Leukemia JO - Leukemia VL - 17 IS - 2 N2 - The anti-CD19 (HD37-dgRTA) and anti-CD22 (RFB4-dgRTA) immunotoxins (ITs) are murine IgG(1) 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. SN - 0887-6924 UR - https://www.unboundmedicine.com/medline/citation/12592332/Treatment_of_SCID/human_B_cell_precursor_ALL_with_anti_CD19_and_anti_CD22_immunotoxins_ L2 - https://doi.org/10.1038/sj.leu.2402790 DB - PRIME DP - Unbound Medicine ER -