Nature Biotechnology pp 1125 - 1132

Scientists have used the deliberate killing of healthy skin cells to eradicate skin cancer in mice. The nonspecific killing of healthy cells is a toxic side effect of conventional chemotherapies, but a team of researchers has turned the (specific) killing of healthy cells into an advantage.

One of the main obstacles in getting the immune system to fight cancer is identifying the peptides or proteins specific to the tumor in order to trigger a therapeutic immune response. Recent studies reveal, however, that the majority of the peptides presented by multiple melanomas (types of skin cancer) and recognized by the immune system arise from proteins that are also expressed in normal melanocytes (the skin's pigment-producing cells). In the September issue of Nature Biotechnology, Richard Vile and colleagues demonstrate how the intentional killing of normal cells (melanocytes) can lead to the eradication of tumor cells (melanoma), thus overcoming the need to identify tumor-specific antigens for melanoma-specific immunotherapy.

The authors intradermally inject mice harboring established tumors with DNA encoding a heat shock protein and a viral enzyme. The viral enzyme promotes specific killing of melanocytes by metabolizing the prodrug ganciclovir to a toxic triphosphate form that damages cellular DNA. Heat shock protein enhances the ability of melanocyte-associated antigens to induce white blood cell mediated killing of melanoma cells. Multiple rounds of treatment resulted in a 100% cure rate. Skin cancer is currently the most common form of cancer in the United States, with about 1 million new cases diagnosed each year.