Researchers at the Burnham Institute for Medical Research at UCSB have made a breakthrough in peptide-based drug delivery, taking another step along a path that may lead to more effective drugs that may produce fewer side effects.
The team, led by Erkki Ruoslahti, distinguished professor at UCSB, found a peptide — or chain of amino acids — that can recognize cancerous tumors and deliver a drug or chemical into them while leaving normal cells alone.
According to Ruoslathi, this peptide, known as iRGD, may be a step toward more effective systems for cancer treatment.
“This peptide has extraordinary tumor-penetrating properties, and I hope that it will make possible substantial improvements in cancer treatment,” Ruoslahti said in a press release. “In our animal studies, the iRGD peptide has increased the efficacy of a number of anti-cancer drugs without increasing their side effects. If these animal experiments translate into human cancers, we would be able to treat cancer more effectively than before, while greatly reducing the side effects the patient would suffer.”
iRGD can bypass a previous barrier earlier findings couldn’t, according to Tambet Teesalu, a staff scientist at the Ruoslathi lab.
“The standard approach has been to attach tumor-homing peptides to drugs or imaging agents, inject them into the bloodstream of tumor mice or patients, the compound then circulates in the blood and the peptide binds to the blood vessels of tumor sites.” Teesalu said. “Usually, the problem is that the payload binds to the blood vessel but [then] just stays there … and doesn’t go in, but we think that we found a solution to deliver drugs beyond the vessel and deep into the tumor.”
According to Teesalu and Kazuki Sugahara, a staff scientist and researcher at the Burnham Institute, the iRGD is unique because of a multi-step mechanism it uses for tumor homing and penetration. After initial binding to a cell surface molecule present on tumor blood vessels, the iRGD peptide is enzymatically clipped by a tumor-derived enzyme called a protease, activating its tumor penetration. As a result, iRGD only targets tumor cells, sparing healthy cells from the drug.
The recent finding, published in the Dec. 8 edition of the journal Cancer Cell, builds upon a series of studies done by the lab regarding peptide-based drug delivery. In August, Ruoslathi — along with Teesalu, Sugahara and Burnham scientist Venkata Ramana Kotamraju — published a paper on the CendR, pronounced “sender,” system in cells, which is a natural process that allows objects to pass through the cell’s barrier using a peptide for activation.
According to Teesalu, the peptide-based targeting system may one day be applied to attack tumors throughout the body.
“Once you know where a tumor is … you might as well use a scalpel and cut it out,” Teesalu said. “With this kind of systemic approach, a smart peptide takes care of finding the tiniest tumor that may metastasize at a site.”
While a large amount of progress has been made, there are many more studies that need to be done before treatments based on the team’s findings will reach the clinic. According to Sugahara, one of the goals of the study is to help produce new treatments for cancer patients.
“With the iRGD and CendR technology, we can deliver about 10 times more of a drug into the tumor,” Sugahara said. “We are trying to develop it further, and our goal is to bring it to the clinic.”