Treatment Uses Antibodies and Light to Target Cancer Cells || NCI Cancer Bulletin for November 15, 2011 - National Cancer Institute

 

Treatment Uses Antibodies and Light to Target Cancer Cells

Researchers from NCI’s Center for Cancer Research (CCR) led by Dr. Hisataka Kobayashi have developed a new type of targeted anticancer treatment using photoimmunotherapy—a light-activated “nano-bomb” bound to a monoclonal antibody (mAb) that delivers the cellular disruptor to tumor cells. In experiments in cells grown in the laboratory and in mouse models, the treatment effectively killed cancer cells that had an excess of a protein targeted by the mAb on their surfaces but spared normal cells. These results were published online in Nature Medicine on November 6.

Traditional photodynamic (light-activated) anticancer therapy uses compounds called photosensitizers that, when exposed to a specific wavelength of light, become activated and trigger cell death. However, in addition to killing cancer cells, photosensitizers can also damage normal tissue. To make the therapy more selective for cancer cells, Dr. Kobayashi and his colleagues created hybrid compounds (conjugates) that consist of a photosensitizer called IR700 bound to one of two mAbs, trastuzumab or panitumumab. These mAbs bind to cell surface proteins called HER2 and HER1, respectively, both of which are overexpressed by some cancer cells.

Cancer cells incubated in a laboratory dish with the conjugates for as little as 1 hour died when exposed to the near-infrared wavelength of light that activates IR700. This rapid action shows that the conjugates only have to bind to the cell surface to kill cancer cells—they do not need to be absorbed by the cell like traditional photodynamic therapy drugs. The conjugates did not kill cells that did not overexpress either HER2 or HER1.

To test the conjugates in an animal model, the researchers established xenograft tumors that overexpressed HER2 or HER1 in mice. After small tumors had formed, the researchers injected the mice with one of the two conjugates and exposed them to near-infrared light 1 day later. Mice that received the treatment had their tumors shrink significantly and lived longer than untreated control mice. The researchers did not observe any toxic effects in normal tissue after 4 weeks of twice-weekly administration of the conjugates.

The fluorescence from the new conjugates may also be useful in noninvasively diagnosing tumors and monitoring response to treatment, explained the authors. “Although more testing will be needed,” said Dr. Kobayashi in a press release, “we believe this [photoimmunotherapy] method has the potential to replace some surgical, radiation, and chemotherapy treatments.”
NCI Cancer Bulletin for November 15, 2011 - National Cancer Institute