What if surgeons could see a color-coded map on tissue, showing them where to work and what to avoid? That’s a goal oncologist Dr. Jim Olson has been trying to make reality for over a decade.
Using a unique molecule called chlorotoxin derived from the venom of the Deathstalker scorpion (L. quinquestriatus), Olson’s team figured out how to make cancer tumors glow. The idea is so exotic that it’s hard to believe, and for many years it was difficult for Olson to find funding for the research. When I first met Olson in 2009, he was busy with new research and another biotech startup, but he lit up, no pun intended, at the opportunity to talk about Tumor Paint. Today, Tumor Paint is in 2 clinical trials in humans, testing it in brain tumors and skin cancer.
Scorpion venoms have been used medicinally for perhaps thousands of years in China and India, but it wasn’t until 1993 that a team at Harvard identified and named chlorotoxin, which by itself is harmless to humans. Chlorotoxin is actually a peptide—a chain of amino acids which may have originally evolved to allow scorpions to paralyze the muscles of cockroaches. The following year, an MD-PhD student at the University of Alabama named Nicole Ullrich (now at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center) theorized and then proved that the newly defined chlorotoxin would bind to glioma brain cancer cells but not normal, healthy cells. This remarkable insight soon resulted in the first experimental cancer treatment, called radiolabeled TM-601, to use the properties of chlorotoxin.
Tumor Paint is a conjugated molecule consisting of the key components of chlorotoxin and Cy5.5, a cyanine dye with fluorescence. Because chlorotoxin has a high affinity for matrix-metalloproteinase (MMP-2), an enzyme which is activated and often upregulated in several virulent cancers, it homes in on cancer cells rather than healthy cells. Olson has found Tumor Paint accumulating in tissue as small as 200 cells, giving it an unusually high level of detail, especially when compared to common scanning methods such as MRI. When near-infrared light is shown on tissue infused with Tumor Paint, the cancerous tissue glows.
In July, 2013, a unique partnership began between the Fred Hutchinson Cancer Center in Seattle and the privately held biotech company Blaze Bioscience, to refine and commercialize Tumor Paint, now called BLZ-100. First Blaze won approval to test BLZ-100 in dogs, where it also found success. Today, BLZ-100 is in 2 human phase I clinical trials trying to determine the ideal dosage. A skin cancer trial is being conducted in Australia and a brain tumor trial in both Australia and the U.S. The U.S. trial, which has already treated half a dozen patients, is being conducted at Cedars-Sinai Medical Center under Dr. Chirag Patil.