Targeted Infrared Photoimmunotherapy for Cancer

Picture displays a photosensitizer molecule joined to an antibody so the complex becomes specific for a cancer cell bearing a receptor for the antibody.  Picture then shows that the new complex binds to a cancer cell and infrared light is applied.  This kills only the cancer cells that have the antibody complex bound.

The photosensitizer IRDye 700DX NHS Ester is linked to a monoclonal antibody against human epidermal growth factor receptor 2 (HER2) or HER1—proteins highly expressed on tumor cells. The IR-Dye-mAb-conjugate binds specifically to the HER2 or HER1 protein on the surface of HER+ cancer cells. Then intense infrared light is applied and kills only the cells that have bound the dye.

A longstanding goal of cancer therapy is the extensive destruction of cancer cells with minimal collateral damage to normal cells. This goal has been very hard to accomplish. Most existing efficacious treatments inevitably inflict collateral damage on nearby normal cells and tissue.

The solution is to find ways to increase the specificity of cancer cell killing. Monoclonal antibodies help with this task.  Using monoclonal antibodies (mAbs) to target proteins that are over-expressed in cancer cells, researchers can preferentially bind cancer cells; however, antibody binding alone does not kill the cell.

Makoto Mitsunaga, Ph.D., a postdoctoral fellow working with Hisataka Kobayashi, Ph.D., and his colleagues in CCR’s Molecular Imaging Program, have improved the mAbs’ ability to kill cancer, at least in mice,  by joining the binding specificity of mAbs with a technique called photodynamic therapy (PDT). PDT uses a photosensitizing agent and the physical energy of light at an appropriate wavelength to kill cells. But conventional PDT lack killing specificity.  Its nontargeted photosensitizers  are taken up by both normal and cancer  cells, so serious side effects can result.  By conjugating mAbs to a photosensitizer, Mitsunaga created a weapon highly specific for mouse cancer cells.   Neighboring toxicity was greatly reduced.  The Kobayashi team recently reported these findings to Nature Medicine.

The team named their new photosensitizing compound IRDye 700DX NHS Ester. Although this photosensitizer distributed itself throughout the mouse’s body, it did no harm unless the dye bound to a cell and intense infrared light was applied. When the IRDye 700DX NHS Ester was linked to a monoclonal antibody against human epidermal growth factor receptors (HER2 or HER1)—proteins highly expressed on tumor cells-—the IR-Dye-mAb-conjugate bound specifically to the HER2 or HER1 protein on the surface of the cancer cells.

Mitsunaga and colleagues also conducted in vitro studies and demonstrated that when the IR-Dye-mAb-cancer-cell-complex was irradiated with near-infrared (IR) light, the cancer cells died rapidly. Infrared light alone or IR-Dye-mAb-conjugate alone did not damage normal cells.  Similar results occurred when mice were treated with the IR-dye-mAb-conjugate  and near-IR light.  Significant tumor shrinkage occurred and survival was prolonged.

This result, while only in mice at this point, shows promise because the IR-Dye-mAb-conjugate killed cancer with improved specificity. If similar results are observed in human studies, targeted infrared photoimmunotherapy may become a high-specificity strategy for killing cancer cells.

Summary Posted: 11/2011

Reference

M Mitsunaga et al. Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. Online Nature Medicine, Nov. 06, 2011, DOI: 10.1038/nm.2554. http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2554.html/ Reviewed by Donna Kerrigan