Credit: Scott Wiseman
JUPITER, FL–April 10, 2018–Christoph Rader, PhD, associate professor at the Florida campus of The Scripps Research Institute, has been awarded a $2.875 million, five-year grant from the National Cancer Institute to develop unique antibody-drug conjugates engineered to eradicate one of the most common forms of leukemia, chronic lymphocytic leukemia (CLL).
"We want to attack the cancer without harming healthy cells and tissues," Rader says. "To do this, we attach a highly potent drug to an antibody and then use the antibody to lead the drug payload to the cellular target."
Doctors diagnose more than 20,000 people a year in the United States with chronic lymphocytic leukemia. The blood cancer originates in a type of white blood cells called lymphocytes, born in bone marrow. As the condition worsens over time, the cancerous cells accumulate, crowding out healthy blood cells. When they move into the blood stream, the malignant cells can spread to other organs and disrupt their healthy function. The illness can cause fatigue, fever and infections, swelling of the lymph nodes and weight loss. More than 4,500 people die each year of CLL in the United States.
The central challenge in fighting all cancers is attacking the malignancy without hurting other parts of the body. Antibodies, the immune system's adaptable targeting system, recognize and bind to specific threats. Using them to attack cancer requires designing ways to attach drug payloads, and then identifying ideal points of attack. Rader's team discovered a binding site on the surface of CLL lymphocytes, called FCMR, which pulls antibodies into the cells in a matter of minutes.
"This particular target is selectively expressed in CLL," Rader says, which means antibodies that bind to the cancer won't attack other, healthy cells.
Attaching the drug payload to the antibody requires a third element, a linking molecule. Working with Scripps Research chemists, including Assistant Professor Hans Renata, PhD, and Professor Emeritus William Roush, PhD, Rader's group has devised several approaches that perform well.
"This draws on the unique interface of biology and chemistry we have here at Scripps Florida. We are creating new molecules with precise designs that are now able to selectively target CLL cells," Rader says. "There is a dire need for the development of new, effective and safe therapies against chronic lymphocytic leukemia."
The grant is number 2R01CA174844-04.
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About The Scripps Research Institute
The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists–including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine–work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see http://www.scripps.edu.
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https://www.scripps.edu/news/press/2018/20180410_leukemia_antibodies.html
