Combined Approach Cures Bladder Cancer in Model

A novel anticancer "photothermal immunotherapy" technique that used lasers and gold nanostars to heat up and destroy tumors in combination with an immunotherapeutic drug cured and immunized mice against bladder cancer in a small proof-of-concept study.

Investigators at Duke University (Durham, NC, USA) had previously described the development of plasmonic gold nanostar particles, which had multiple sharp spikes that were able to capture laser energy more efficiently. In the current study, gold nanostar therapy was combined with an immunotherapeutic drug that inhibited the activity of PD-L1 (Programmed death-ligand 1), which would otherwise disable cancer-destroying T-cells.

In the current proof-of-concept study, MB49 bladder cancer cells were injected into the hind legs of a group of mice. After tumors began to grow, the animals were treated in one leg only with gold nanostars and laser heating, nanostars plus PD-L1 inhibitor, or PD-L1 inhibitor alone. A group of control animals were not treated.

Results published in the August 17, 2017, online edition of the journal Scientific Reports revealed that animals receiving no treatment rapidly died from cancer, as did those receiving only the gold nanostar phototherapy, since the treatment did nothing to affect the tumor growing in the untreated leg. In contrast, some animals responded well to the immunotherapy alone, with the drug slowing growth of both tumors, but none survived more than 49 days. However, animals in the group treated with both the immunotherapy and the gold nanostar phototherapy fared much better, with two of the five mice surviving more than 55 days.

The investigators referred to the two-pronged treatment approach as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY). Using this combination of immune-checkpoint inhibition and plasmonic gold nanostar–mediated photothermal therapy, they were able to achieve complete eradication of primary treated tumors and distant untreated tumors in some mice implanted with the MB49 bladder cancer cells. Delayed rechallenge of mice cured by SYMPHONY with injections of MB49 cancer cells 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 nanostar spikes work like lightning rods, concentrating the electromagnetic energy at their tips," said senior author Dr. Tuan Vo-Dinh, professor of chemistry and biomedical engineering at Duke University. "We have experimented with these gold nanostars to treat tumors before, but we wanted to know if we could also treat tumors we did not even know were there or tumors that have spread throughout the body. When a tumor dies, it releases particles that trigger the immune system to attack the remnants. By destroying the primary tumor, we activated the immune system against the remaining cancerous cells, and the immunotherapy prevented them from hiding."

"The ideal cancer treatment is non-invasive, safe, and uses multiple approaches," said Dr. 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 would truly have a cure."

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