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Photoimmunotherapy ‘Bursts’ Tumors, Spares Nearby Cells

Targeted laser light causes molecular-level explosions

Kerstin Stenson, MD, director of Rush University Medical Center’s Head and Neck Cancer Program, is treating patients with photoimmunotherapy (PIT), an experimental technique that combines the immune system’s ability to target cancer cells with the ability of laser energy to destroy those cells. Like a high-tech weapon in a spy thriller, PIT delivers precise, lethal payloads with a minimum of collateral damage.

“This treatment is so unique and promising because its cancer cell-killing power is so selective and immediate,” Stenson said. “It really is just like a guided missile.”

PIT expands on photodynamic therapy, a two-step process that starts with a patient being injected with a photosensitizing drug that’s designed to accumulate in and near a cancerous tumor. Then doctors beam specific wavelengths of light at the tumor, causing the absorbed photosensitizer to produce a form of oxygen that kills nearby cells.

In PIT the photosensitizer is combined with a monoclonal antibody that specifically targets and binds with receptors found only on the surface of head-and-neck cancer cells. Administered intravenously, the photosensitizer/antibody combination—referred to as a “payload drug”—circulates throughout the patient’s body but attaches only to head-and-neck cancer cells.

The next day, Stenson affixes tiny laser-optic fibers near the surface of the tumor. If the tumor is difficult to reach, she threads the fibers through small catheters directly into the tumor. Then the laser-light energy is beamed through the fibers, hitting the photosensitizer target. The laser sets off molecular-level explosions that weaken the cancer cell walls, allowing water molecules contained in the surrounding tissue to rush in until the cancer cells burst.

“Almost immediately, you can see the tumor start dying. It turns white and melts away,” Stenson said. Because the payload drug remains inert unless activated by a specific wavelength of light that doesn’t damage human tissue, destroying the cancer cells causes almost no damage to surrounding cells. “The drug/dye combination––the monoclonal antibody combined with the photosensitizer––is not toxic until activated by near infrared light; thus, it is very safe from a systemic perspective,” Stenson explained.

In comparison, patients treated with conventional photodynamic therapy must avoid strong sunlight for several months because tiny amounts of photosensitizer that remain in their systems could be activated by the sunlight, causing severe sunburn.

Stenson is leading a clinical trial that is testing the safety and effectiveness of PIT for patients whose head-and-neck cancer has not responded to radiation or chemotherapy, or when surgery is not feasible because of a tumor’s location.

“Getting inside the cancer cell means we can get systemic treatment locally more than any other treatment,” she said.

The new study is being funded by Aspyrian Therapeutics, the biotechnology firm that created the monoclonal antibody conjugate (RM-1929) and secured the exclusive license for the technology from the National Cancer Institute, which developed PIT.

Beyond the potential of PIT as an effective therapy for patients with head-and-neck cancer, the system may be useful in other forms of cancer and as part of combination treatment with immune-modulation chemotherapy. “We hope that once we prove the safety and effectiveness of this treatment specifically for head-and-neck cancer, the photosensitizer could be combined with immune-stimulating drugs that target other forms of cancer,” Stenson said.

Because PIT therapy appears to work quickly and precisely, it may also have potential when combined with surgery. Even when a cancer surgeon successfully removes a cancerous tumor, some cancer cells invariably remain in the surrounding tissue with the ability to metastasize, which is why cancer surgery often is followed by chemotherapy. Since surgery makes those areas temporarily accessible, PIT’s one-two punch of light energy-activated, targeted therapy might greatly reduce the chance that the cancer redevelops, Stenson noted.

Source: Rush University Medical Center; October 14, 2016.

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