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

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.

journal_name

Leuk Res

journal_title

Leukemia research

authors

Kachlany SC,Schwartz AB,Balashova NV,Hioe CE,Tuen M,Le A,Kaur M,Mei Y,Rao J

doi

10.1016/j.leukres.2009.08.022

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

777-85

issue

6

eissn

0145-2126

issn

1873-5835

pii

S0145-2126(09)00429-9

journal_volume

34

pub_type

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