Scientists at Duke University say they have combined a cancer immunotherapeutic with nanotechnology to improve the efficacy of both therapies in a mouse study. They published their work, "Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) for the Treatment of Unresectable and Metastatic Cancers," in Scientific Reports.
The new approach also attacked satellite tumors and distant cancerous cells, leading to two mice being cured of the disease and one being vaccinated against it.
Using a combination of immune-checkpoint inhibition and plasmonic gold nanostar (GNS)-mediated photothermal therapy, we were able to achieve complete eradication of primary treated tumors and distant untreated tumors in some mice implanted with the MB49 bladder cancer cells, wrote the investigators. Delayed rechallenge with MB49 cancer cells injection in mice that appeared cured by SYMPHONY did not lead to new tumor formation after 60 days observation, indicating that SYMPHONY treatment induced effective long-lasting immunity against MB49 cancer cells.
"The ideal cancer treatment is noninvasive, safe, and uses multiple approaches," said Tuan Vo-Dinh, Ph.D., the R. Eugene and Susie E. Goodson Professor of Biomedical Engineering, professor of chemistry, and director of the Fitzpatrick Institute for Photonics at Duke University. "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 specific photothermal immunotherapy was developed by Duke researchers and uses lasers and gold nanostars to heat and kill tumors in combination with an immunotherapeutic drug. The technique works based on the ability of nanoparticles to accumulate preferentially within a tumor due to its leaky vasculature, according to the scientists, who add that gold nanostars have the advantage of geometry. With many sharp spikes, they can capture the laser's energy more efficiently, thus permitting them to work with less exposure, making them more effective deeper within a tissue.
"The nanostar spikes work like lightning rods, concentrating the electromagnetic energy at their tips," said Dr. Vo-Dinh. "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."
Dr. Vo-Dinh explained that the body's immune system protects against the growth of cancerous cells. Many tumors, however, overproduce the programmed death-ligand 1 (PD-L1) molecule, which disables T cells so they cannot attack the tumor. A number of drugs are being developed to block the action of PD-L1.
In the study, the Duke team injected bladder cancer cells into both hind legs of a group of mice. After waiting for the tumors to grow, the researchers explored a number of therapies, but only on one of the legs.
Those that received no treatments all quickly succumbed to the cancer, as did those receiving only the gold nanostar phototherapy, because the treatment did nothing to affect the tumor in the untreated leg. While a few mice responded well to the immunotherapy alone, with the drug stalling both tumors, none survived more than 49 days.
The group treated with both the anti-PD-L1 immunotherapy and the gold nanostar phototherapy fared much better, with two of the five mice surviving more than 55 days.
"When a tumor dies, it releases particles that trigger the immune system to attack the remnants," said Dr. Vo-Dinh. "By destroying the primary tumor, we activated the immune system against the remaining cancerous cells, and the immunotherapy prevented them from hiding."
According to Dr. Vo-Dinh, one mouse is still alive almost a year out with zero recurrence of the cancer. When more cancerous cells were injected, the mouse's immune system attacked and destroyed them, demonstrating a vaccine effect in the cured mouse.
The Duke team has plans to follow up with larger cohorts of mice and to work with other clinical researchers to test the treatment on mouse models of brain, breast, and lung cancers.
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