Anti-leukemia activity of a bacterial toxin with natural specificity for LFA-1 on white blood cells

Scott C. Kachlany, Amy B. Schwartz, Nataliya V. Balashova, Catarina E. Hioe, Michael Tuen, Amy Le, Manpreet Kaur, Yongyi Mei, Jia Rao

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

The oral bacterium, Aggregatibacter actinomycetemcomitans, produces a leukotoxin (LtxA) that is specific for white blood cells (WBCs) from humans and Old World primates by interacting with lymphocyte function antigen-1 (LFA-1) on susceptible cells. To determine if LtxA could be used as a therapeutic agent for the treatment of WBC diseases, we tested the in vitro and in vivo anti-leukemia activity of the toxin. LtxA kills human malignant WBC lines and primary leukemia cells from acute myeloid leukemia patients, but healthy peripheral blood mononuclear cells (PBMCs) are relatively resistant to LtxA-mediated cytotoxicity. Levels of LFA-1 on cell lines correlated with killing by LtxA and the toxin preferentially killed cells expressing the activated form of LFA-1. In a SCID mouse model for human leukemia, LtxA had potent therapeutic value resulting in long-term survival in LtxA-treated mice. Intravenous infusion of LtxA into a rhesus macaque resulted in a drop in WBC counts at early times post-infusion; however, red blood cells, platelets, hemoglobin and blood chemistry values remained unaffected. Thus, LtxA may be an effective and safe novel therapeutic agent for the treatment of hematologic malignancies.

Original languageEnglish
Pages (from-to)777-785
Number of pages9
JournalLeukemia Research
Volume34
Issue number6
DOIs
StatePublished - Jun 2010
Externally publishedYes

Keywords

  • Acute myeloid leukemia
  • Immunotoxin
  • Lymphoma
  • Targeted therapy

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