Abstract

Leukemia is a serious white blood cell cancer that more than 44,000 Americans develop every year.  Currently there are approximately 218,000 people in the U.S. living with the disease, and each year 21,000 people die from leukemia.  While advancements have been made in the diagnosis and treatment of leukemia, the 5-year survival rates for many forms of the disease remain relatively low and have changed little over the last 20 years.  Thus, there is a great need to identify newer therapeutics with greater activity and less side effects.  Bacterial toxins have been used as anti-cancer agents and represent a new class of targeted therapeutics.  The bacterium, A. actinomycetemcomitans produces a leukotoxin that has specificity for certain white blood cells.  Preliminary in vitro studies with leukotoxin indicate that it could be an effective anti-leukemia therapeutic with high specificity.  Leukotoxin targets LFA-1-expressing cells and studies have shown that LFA-1 is over-expressed on several lymphomas and leukemias, indicating that malignant cells would be more susceptible to killing by leukotoxin than normal white blood cells.  Recent experimental evidence supports the notion that leukotoxin might be an effective targeted therapy for the treatment of hematologic malignancies.  Studies show that leukotoxin is not toxic towards non-hematopoietic cells (ie. epithelial, endothelial, liver cells), leukotoxin is not degraded or inactivated in a liver biotransformation model system (HepG2 cells), and leukotoxin is highly active in whole blood towards leukemia cells.