Cancer Research

Fighting Cancer with Killer Cells

Novel immunotherapy uses three immune mediators

29.1.2013 | Natural killer cells are part of the body's immune system and can effectively fight cancer. Unfortunately, they quickly lose their aggressiveness and are no match for solid tumors. A new approach at the German Cancer Research Center enhances their effectiveness radically.
Fighting cancer using the body's own defense system is a promising treatment approach. Immune therapies have become clinical routine in treating cancers such as malignant melanoma and prostate cancer. Natural killer cells, or NK cells, are considered to be particularly suitable weapons against cancer. They are part of the innate immune system and respond to a wide range of cancer cells of diverse origin. Moreover, NK cells also kill tumor cells that have lost a specific target and go unnoticed by other immune cells.

"The big problem in using NK cells for therapy is their rapid loss of activity, hence their aggressiveness", Dr. Adelheid Cerwenka explains. Together with her team at the German Cancer Research Center DKFZ, Cerwenka is trying to develop cancer therapies based on NK cells. "Although there are good treatment results for certain types of blood cancer, NK cells have been clinically effective in fighting solid tumors only in a few cases", the immunologist elaborates.

Cerwenka's team has now discovered a "cocktail" consisting of three different immune mediators that enables NK cells to remain active over long periods of time. These mediators are the interleukins 12, 15, and 18. NK cells that were activated in the culture dish and then injected into cancerous mice significantly slowed down tumor growth. The animals survived significantly longer, and in one quarter of animals the tumors even regressed completely. The NK cells pretreated with the cocktail initially multiplied strongly in the mice. The researchers found it particularly remarkable that the NK cells appear to be re-stimulated by other immune cells in the bodies of the affected mice and were thus kept in an active state. Even after three months, the DKFZ immunologists still found active, functional NK cells in mice, even after the tumors had already been rejected. "We previously thought immunological memory exists only in cells of the adaptive immune system", Cerwenka explains.

However, NK cells were only able to let tumors shrink if the mice had undergone prior radiation treatment. The scientists found a lot more NK cells near the tumor tissue in irradiated mice than in the control animals. Cerwenka and her colleagues do not yet know the precise molecular reason for this. "The good thing is that we might be able to achieve this effect in a potential clinical application by combining the cocktail-treated NK cells with radiation therapy", the immunologist hopes. Furthermore, human NK cells treated with this "cocktail" also display all molecular signs of sustained activation in cell cultures. Cerwenka and her team have already started testing the effectiveness of killer cells in fighting human cancer cells. "We hope to advance the development of NK cell therapies against cancer with our novel approach", Cerwenka summarises.

  (© German Cancer Research Center DKFZ / AcademiaNet)
Dr. Sibylle Kohlstädt

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Source

  • Jing Ni, Matthias Miller, Ana Stojanovic, Natalio Garbi und Adelheid Cerwenka: Sustained effector function of IL-12/15/18 preactivated NK cells against established tumors. Journal of Experimental Medicine 2012, DOI: 10.1084/jem.20120944

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