Cornell team finds success sending 'cancer-killing machines' through bloodstream

January 14th, 2014

Cornell team finds success sending 'cancer-killing machines' through bloodstream

Written by D.W. Nutt

6:57 PM, Jan 13, 2014 |

Ithaca Journal.com - for full article


 ITHACA —Biomedical engineers at Cornell University are turning sticky nanoparticles into “cancer-killing machines” to prevent cancer cells from spreading throughout the body. 

The groundbreaking research could one day pave the way for eliminating 90 percent of cancer deaths.

 The research team, which recently published its findings in Proceedings of the National Academy of Sciences, is led by Cornell professor of biomedical engineering Michael King. His team began their research about 4½ years ago.

 “About two years into the project we really realized what we’ve been sitting on and just how remarkable this approach was,” said King, of Ithaca. “Most drug delivery strategies, the easiest thing to do is kill cancer cells, for instance, that are sitting in a test tube by themselves. But we have a very different type of technology where we put these nanoparticles into the blood and it works far better in the complicated environment of flowing blood than it ever did in a dish or a test tube. It’s fairly unique in that respect.”

 The process is designed to combat metastasis, in which invasive cancer cells from a primary tumor migrate through tissue and spread to distant organs via the bloodstream.

 “Metastasis is responsible for most cancer deaths. If you can control it or prevent it then most cancers will basically be treatable,” King said. “If prostate cancer is localized to the prostrate then there are ways to surgically, or with medications, take care of that, typically. A major route for cancer spreading is of course through the circulation. And that’s the phenomenon we’re trying to interrupt or prevent.”

 King and his team’s solution was to design nanoscale liposomes, or particles, that have two proteins attached to their surface: E-selectin and TRAIL.

 E-selectin is an adhesive molecule that can bind to other cells. TRAIL is a therapeutic protein made by immune cells that can program cancer cells to die off upon contact, a process called apoptosis. Together they make a tag-team effort: one protein to stick, one to kill.

 When these nanoparticles are introduced into the bloodstream they stick to and cover all the white blood cells, basically piggybacking on them. If a cancer cell makes its way into the blood and bumps into one of these modified white blood cells, it will die by apoptosis.

 “All they have to do is bump into cancer cells to kill them, and in the chaotic environment of blood flow it works remarkably well,” King said. “These interactions are occurring nonstop.”

 The blood flow actually accelerates the process, King said, and within about two hours the cancer cells have disintegrated, with no adverse effects appearing in the white blood cells or the cells that line the blood vessels.

 “It’s not like they’re reprogramming the white cells. The white cells can go about their business. It just so happens that if any cancer cell is unlucky enough to bump into it, it’s toast,” King said.

 Innovations in cancer fight

 King’s group consists of 10 Ph.D. students, another half-dozen staff members, as well as several undergraduate students. King said about two-thirds of the group is focused on the cancer metastasis project.

 “It’s a a real smart team,” he said.

 The project grew out of a larger initiative started by the National Cancer Institute in 2009, when it created 12 Physical Sciences-Oncology Centers that would bring together engineers and physical scientists with cancer biologists and oncologists to find new ways to tackle cancer. Cornell’s Center on the Microenvironment and Metastasis is part of the 12-university PS-OC network. King serves as one of three project leaders at CMM, which helped fund his team’s study.

 “We’ve been very fortunate to be part of that,” King said. “This is kind of a culmination of that work.”

 King said he’s not aware of any other kind of treatment that uses collisions in the blood flow to neutralize cancer cells and he’s hopeful the concept can be applied to other diseases, too.

 King’s team has successfully tested the procedure in human blood samples as well as live mice, targeting colon and prostate cancer cells. The researchers are working on longer-term animal experiments with the ultimate goal of reaching human clinical trials, but that could be several years away, King said.

 In the meantime his research has garnering a great deal of attention from the scientific community and beyond.

 “We’ve been getting great some feedback and certainly the story has caught on, even internationally. I’ve been contacted by researchers, well wishers, in many cases cancer patients or relatives of cancer patients who are curious about what stage the research is at and how long they have to wait, basically. And that’s very poignant,” King said. “We try to be very careful about how we represent the work and not overstate what stage the research is at. The response we’ve gotten so far has also been very encouraging, and we kind of know we’re on the right track here.”