Using near-infrared light to kill cancer cells in mice
Researchers have gained critical insights into how the shape of near-infrared immunotherapy agents work. When embedded in the membrane of a cancer cell, exposure to light causes the drug to dramatically change shape, scratching the protective casing of the cancer cells and causing them to die very quickly.
Researchers at NCI’s Center for Cancer Research have found that a technique called near-infrared immunotherapy for treating cancer has the potential to kill cancer cells in record time, essentially destroying them with the flick of a light switch. Scientists were not certain of the underlying mechanisms of this approach, but they succeeded in elucidating this technique in detail at the cellular and molecular level, gaining insights that could help scientists further boost the effectiveness of the novel treatment. The laboratory and mouse findings, by Hisataka Kobayashi, M.D., Ph.D., Senior Investigator in the Molecular Imaging Program, and colleagues appeared November 6, 2018, in ACS Central Science.
Near-infrared immunology is an emerging technique for treating cancer that is already being studied in clinical trials. It involves identifying a protein, called an antibody, that recognizes and targets a specific type of cancer cell. The antibody is joined to a compound that’s sensitive to light and then administered to a patient. Within the body, the drug seeks out and attaches to only cancer cells, not healthy ones. Next, doctors apply a beam of infrared light to the cancer site, either externally or directly using a fiber optic needle, which activates the drug and causes the cancer cells to die. Research by Dr. Kobayashi and his colleagues reveals new details into how this cell death occurs.
To learn more about the molecular mechanisms of this phenomenon, they studied the effects of a near-infrared immunotherapy agent called antibody-IR700 on a plate simulating human cancer cells in a petri dish using sophisticated microscopes. The researchers discovered that exposure to near-infrared light causes the immunotherapy agent to dramatically change its form from Y-shaped to globular. When it is embedded in the cell membrane of a cancer cell, this warping causes scratches along the protective casing of the cell. Once enough scratches occur, liquid bursts through the cell’s membrane, causing the cell to rupture in less than a minute following exposure to the light.
The researchers also studied this technique in a mouse with multiple tumors, applying different amounts of light intensity to each tumor. They found that higher light intensity resulted in more cancer cells being eliminated. Also in mice, they detected the “leftovers” of the immunotherapy agent in the mouse’s urine just hours after near-infrared light was applied to the cancer site – a strong indication that the cancer cells were killed.
Dr. Kobayashi notes that this technique doesn’t just target cancer cells or boost the immune system to attack cancer cells – it does both. “All the cell’s proteins and even its DNA are exposed to the immune system. The immune system will recognize that [the proteins and DNA are] coming from the dying cell, and then the immune system will react only to the dying cancer cells,” he explains.
Near-infrared immunotherapy could be applied to any type of cancer if the right antibody is identified and used. In this study, the researchers analyzed the near-infrared immunotherapy agent IR-700, which is about to be tested in phase III clinical trials for head and neck cancer.
Although the concept of near-infrared immunotherapy is compelling, understanding why it works is critical for a number of reasons. Kobayashi explains, “Based on these new insights, we might be able to design a new, superior IR700 that would be improved in many respects, such as activation wavelength, stability and cytotoxic efficacy.”Summary Posted: Thu, 11/01/2018