TSRI scientists receive NIH grant to create new drug for chronic lymphocytic leukemia

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have been awarded more than $1.4 million from the National Cancer Institute of the National Institutes of Health to create a potential new drug to attack the malignant cells that cause chronic lymphocytic leukemia (CLL), which is the most common leukemia in the Western world.

Christoph Rader, a TSRI associate professor, will be principal investigator of the new three-year study. William Roush, a TSRI professor, associate dean of graduate studies and executive director of medicinal chemistry, will be co-principal investigator.

CLL affects approximately 150,000 patients and causes 4,500 deaths per year in the United States alone. While chemotherapy and radiation are used to treat this slow growing form of leukemia, currently there are no therapeutic options for the disease in which physicians can selectively target the malignant cells yet spare normal cells and tissues.

The scientists plan to use the recently discovered cell surface receptor TOSO, which is overexpressed in leukemia cells, to create a rapid and effective entry point for delivering drugs to these malignant cells while bypassing normal cells as much as possible.

"We want to create carrier-payload combinations to deliver cytotoxic drugs with very specific targeting," Roush said. "Once we have accomplished that, we expect to optimize potency."

In addition, the team plans to use an antibody fragment to add a second target to the treatment—the receptor tyrosine kinase ROR1, which is expressed exclusively on leukemia cells.

"This dual-targeting strategy will lay the foundation for further preclinical and clinical investigations in the treatment of this form of leukemia," said Rader. "We also think that the novel biological and chemical components that come from this study can be easily exploited to develop combinations for diseases beyond CLL."