Research points to potential new treatment
Stealthy and stubborn, ovarian cancer is a particularly vexing malignancy, difficult to diagnose in its early stages and difficult to treat once it progresses. However, research at Fox Chase is focusing on one of the most promising new approaches to dealing with the disease—using engineered antibodies to target tumor cells while leaving healthy cells intact.
Gregory P. Adams, co-leader of the research program in developmental therapeutics, and his colleagues recently isolated a small, antibody-like molecule called GS45 that is capable of zeroing in on a red flag, of sorts, that distinguishes ovarian cancer cells from normal ones.
The molecule targets a receptor called the Müllerian Inhibiting Substance Type II Receptor, or MISIIR, which is scarce in normal tissue but more abundantly present on the surface of human ovarian cancer cells.
“A problem with targeted therapies is that many of the targets found on cancer cells are also found on normal cells,” says Tatiana Karakasheva, a member of the Adams lab who presented the research in April at the annual American Association for Cancer Research meeting. “When you direct cell-killing drugs at those targets, you get side effects. The great thing about this target is that it’s primarily restricted to the reproductive system, and its expression dramatically increases in ovarian cancer.”
Research at Fox Chase is focusing on a promising new approach to dealing with ovarian cancer.
But finding antibodies that would home in on and bind to the receptor was a challenge. Using a method in which human antibody fragments are expressed and selected on the surface of viruses that infect bacteria, Karakasheva and Adams managed to isolate a group of candidates, including GS45.
The researchers then engineered the fragments into full-size antibodies that can be used in further experiments. They plan to first demonstrate that GS45 does, indeed, selectively target ovarian cancer cells; then explore its potential for cancer treatment by attaching a drug to it.
The scientists will be working with mice, but as Adams explains, “because mouse and human MISIIR are almost identical, whatever the mouse experiments reveal about targeting and toxicity is likely to apply to humans. That puts us in a powerful position to move this work forward through additional pre-clinical studies and, if it continues to show promise, to clinical trials.”