Double-barreled attack shows potential in quest for cancer vaccine

In experiments on mice, researchers at Duke University have found that combining two different techniques for fighting cancer is more effective than either treatment is on its own. In one case, the mouse's immune system not only destroyed the tumor, but stayed strong enough to ward off a later injection of cancer cells, raising hopes that the strategy could one day lead to a viable cancer vaccine.

The two techniques used in the new study take very different approaches to combat cancer. One is a drug that blocks the production of PD-L1 – molecules produced in great numbers by tumors that attack and kill T cells, the foot-soldiers of the immune system.

The second is called photothermal therapy, which is based around star-shaped nanoparticles made of gold. These nanostars are injected into the patient, where they tend to cluster inside tumors, and once there, they're blasted with lasers from outside the body. That heats up the gold and roasts the cancer cells from the inside. Golden nanostars have been used in the past to deliver drugs right into the heart of tumors, but in this case that all-important shape helps capture the energy of the laser more efficiently.

"The nanostar spikes work like lightning rods, concentrating the electromagnetic energy at their tips," says Tuan Vo-Dinh, lead author of the study. "We've experimented with these gold nanostars to treat tumors before, but we wanted to know if we could also treat tumors we didn't even know were there or tumors that have spread throughout the body."

To do so, they paired this technique with an immunotherapy drug designed to combat bladder cancer, to create a combined treatment they call photothermal immunotherapy. To test the treatment, the team injected bladder cancer cells into both hind legs of mice, and waited for tumors to develop. Once they did, the researchers administered different treatments to different groups of mice, but only on one leg – they wanted to see which therapies, if any, would be able to clear the whole body of cancer.

Unsurprisingly, the control group, which received no treatment, all died fairly quickly. A group that was treated with the golden nanostars also didn't last long, because this direct attack left the tumor in the other leg unaffected. Meanwhile, some mice treated with the PD-L1-blocking drug fared better, because the drug circulates through the body. Even so, the survival rate topped out at 49 days.

But when both the immunotherapy and the gold nanostars were used in tandem, survival rates shot up. Two of the five mice that were tested survived for longer than 55 days – one of which is still kicking almost a year after the treatment. The combination appears to be effective because the nanostar therapy is a targeted attack that wipes out a single tumor, while the drug then mops up the stragglers that might be hiding in other parts of the body.

"When a tumor dies, it releases particles that trigger the immune system to attack the remnants," says Vo-Dinh. "By destroying the primary tumor, we activated the immune system against the remaining cancerous cells, and the immunotherapy prevented them from hiding."

The most impressive part is that a month after the initial treatment, the researchers injected more cancer cells into the animal and found that the mouse's immune system was still fired up, destroying the new cancer and effectively providing a vaccine effect.

While the study only involved a fairly small group of mice, it's a promising start. The researchers plan to test the technique on other forms of cancer, in the hopes of one day using it to develop a vaccine.

"The ideal cancer treatment is non-invasive, safe and uses multiple approaches," says Vo-Dinh. "We also aim at activating the patient's own immune system to eradicate residual metastatic tumors. If we can create a long-term anticancer immunity, then we'd truly have a cure."

The research was published in the journal Scientific Reports.

Source: Duke University