Most cancer research focuses on the mechanisms of tumor development, despite the fact that tumor metastasis—the spread of tumor cells—is responsible for approximately 90 percent of cancer deaths. The team in the lab of professor Michael King at Cornell’s Meinig School of Biomedical Engineering has made a breakthrough discovery that could change the focus of cancer treatment by targeting the cells that lead to metastasis. Their study, published today in the Journal of Controlled Release, shows that a protein they engineered to fit onto nanoparticles successfully kills tumor cells in the bloodstreams of mice with prostate cancer.
King’s lab engineered tiny lipids called liposomes, which are approximately one-one-hundredth the size of white blood cells, with a protein known as TRAIL (tumor necrosis factor related apoptosis-inducing ligand) to create the nanoparticles. Once they are injected into the bloodstream, TRAIL proteins attach to white blood cells, called leukocytes, as they travel through the bloodstream and kill the cancer cells.
“When we made these particles and introduced them to the bloodstream of the mice we were able to kill all the cancer cells in blood flow within a couple hours. This therapeutic worked so well, it was like a key fitting a lock. It solved the puzzle,” King tells mental_floss.
Mice in the control groups (“Buffer” and “ES”) showed widespread metastasis to internal organs, as indicated by the color map. In contrast, mice treated with E-selectin/TRAIL liposomes (“ES/T”) showed no spread of cancer to the other organs—as well as a reduction of the tumor burden in the prostate. Image credit: Wayne et al. in Journal of Controlled Release
King’s lab had previously been studying ways to kill cancer cells by getting the cells to adhere to a medical device, which killed them. “Our breakthrough was, instead of making medical device surfaces toxic to cancer cells, we took the adhesion TRAIL molecules and put them on the surface of nanoparticles," he says. "When we flipped the geometry like that, and injected those proteins into the bloodstream or lymphatic system, we had really astounding success.”
To test the protein’s cancer-killing abilities, cancerous cells were surgically introduced into the healthy mice, giving them prostate cancer. When the mice developed tumors in their prostates big enough for researchers to feel and see, tumor cells began to release into the blood and move throughout the body, which “is what happens in human disease as well,” says King.
Their hope was that injecting TRAIL into the bloodstream and lymphatic systems of the mice would prevent new tumors forming in distant organs. The results were even better than that. “It was a total success. It prevented metastases, and shrunk the original tumor in size, which we weren’t even expecting. That was a bonus,” King says.
A chart showing the organization of the study. They started treatment on the mice three weeks after tumor implantation and repeated it every three days until the endpoint of the trial, at nine weeks. The mice were imaged once per week to track tumor growth. Image credit: Wayne et al. in Journal of Controlled Release
The TRAIL treatment is promising as a cancer therapeutic in humans, says King, because the protein is a natural product made by immune cells and has already been tested in humans. “We just make more of it and put it in the right place. It’s very well tolerated by human patients, with no side effects,” he says. “Dosages that we use in our system to completely prevent metastases are 1% of the dosages that have already been safely used in humans. We anticipate no adverse effects.”
They believe it has great potential as a therapy in association with cancer-removal surgeries or biopsies. “We think maybe just one dose before surgery and one or more dosages after surgery could have a noticeable and very successful suppression or prevention of metastases,” says King. “That’s something we still need to prove with animal trials. Any intervention, even needle biopsy, is a potential route for disseminating tumor cells all over the body. Scheduled surgery is a situation where you know when that event will occur so why not time it perfectly with a small number of doses.”
Their next study will look at treating metastasis in breast cancer using a mouse model. “We would be treating the mouse exactly the way the human disease would be treated, so that would be very convincing if we are successful.”