Immune Cells Sleep No More
Johns Hopkins scientist Charles Drake is testing a unique molecule for its ability to awaken the immune system’s ability to recognize and destroy prostate cancer cells. This molecule is a key protein that acts as a sleep-aid to soldiering immune cells.
“T-cells are designed to kill specific targets by punching holes in the cell’s outer layer or by instructing them to self-destruct,” says Charles Drake, M.D., Ph.D., assistant professor at the Johns Hopkins Kimmel Cancer Center. “But when a tumor emerges, T-cells are asleep while on duty and fail to eradicate the malignant cells.”
According to Drake, one way that T-cells are put to sleep is by a protein called LAG-3 which is on the outer surface of the cells. The precise trigger for activating LAG-3 has not yet been found, but studies show that the protein can be blocked, re-awakening these non-functional T-cells.
Reporting in the November 2007 issue of the Journal of Clinical Investigation, Drake and his team added a LAG-3 blocking antibody to an immune-stimulating vaccine for prostate cancer in mice bred to develop treatment-resistant disease. The experiment resulted in a four-fold increase in the number of activated T-cells that migrated into the prostate compared with mice that received the vaccine alone.
“With the vaccine alone, T-cells hover along the tumor’s perimeter,” notes Drake. “But when we blocked LAG-3, they migrated to the center of the tumor.” His team also found that mice receiving the vaccine plus LAG-3 blockade had tumors that were less well-developed, less aggressive, with lower Gleason scores.
The Drake laboratory is continuing studies to figure out exactly how LAG-3 turns down T cell function, and also is looking for LAG-3 blocking agents that will work in humans
Dr. Drake is a Damon Runyon Lilly Clinical Investigator; this research was further supported by the National Institutes of Health and gifts from William and Betty Topercer, Dorothy Needle, Jack Goldsmith, and the Janey Fund.
In addition to Drake, study participants include Joseph F. Grosso, Cristin C. Kelleher, Timothy J. Harris, Charles H. Maris, Edward L. Hipkiss, Angelo De Marzo, Robert Anders, George Netto, Derese Getnet, Tullia C. Bruno, Monica V. Goldberg, Drew M. Pardoll from Johns Hopkins.
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