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," says Dr. Adelheid Cerwenka. 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 explains.
Cerwenka's team has now been the first to enhance the NK cells' deadly potential in mice using a cocktail of three different immune mediators (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. By contrast, NK cells without prior treatment were ineffective.
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," says Cerwenka.
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 at their site of action in tumor tissue in irradiated mice than in control animals. Cerwenka and colleagues do not yet know the precise molecular reason for this observation. "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."
Cocktail-treated human NK cells also display all molecular signs of sustained activation in cell culture. Adelheid 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," says Cerwenka.
Jing Ni, Matthias Miller, Ana Stojanovic, Natalio Garbi and 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
*The body's defense system is made up of the innate and the adaptive immune systems. The innate system is responsible for immediate defense of the body. Cells of the innate system do not have specific receptors but respond to a broad spectrum of pathogens (using phagocytes, granulocytes) or transformed body cells (using NK cells). By contrast, T and B lymphocytes, which are part of the adaptive immune system, are equipped with highly specific receptor molecules directed against protein components of specific pathogens. If these long-lived cells, which form a sort of memory of the immune system, encounter this specific invader again, they first have to multiply before they can mount an effective defense. Therefore, several days pass before the adaptive immune defense is ready to fight the attack.
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 2,500 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg where promising approaches from cancer research are translated into the clinic. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. The center is a member of the Helmholtz Association of National Research Centers. Ninety percent of its funding comes from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.
Dr. Sibylle Kohlstädt | Source: EurekAlert!
Further information: www.dkfz.de
Further Reports about: aggressiveness > cancer cells > Cocktail > Deutsches Krebsforschungszentrum > DKFZ > German language > immune cell > immune system > immunological memory > risk factor > tumor cells > tumor growth
More articles from Health and Medicine:
Canadian researchers lead groundbreaking discovery in deadly childhood cancer
11.12.2013 | McGill University Health Centre
Review Calls for Increased Attention to Cancer Risk from Silica
11.12.2013 | American Cancer Society
The molecular architecture of three key proteins and their complexes reveals how plants fine-tune their immune response to pathogens
Plants rarely get sick in their natural environment. When the threat of infection arises, a quick decision is made about the necessary countermeasures. The course is set by a protein which forms complexes with its partner proteins for this purpose.
Jane Parker from the Max Planck Institute for Plant Breeding ...
Researchers studying speciation of butterfly orchids on the Azores have been startled to discover that the answer to a long-debated question "Do the islands support one species or two species?" is actually "three species".
Hochstetter's Butterfly-orchid, newly recognized following application of a battery of scientific techniques and reveling in a complex taxonomic history worthy of Sherlock Holmes, is arguably Europe's rarest orchid species. Under threat in its mountain-top retreat, the orchid urgently requires conservation recognition.
A lavishly illustrated publication, titled "Systematic revision of Platanthera in ...
Researchers from Brown University and the University of Hawaii have found some mineralogical surprises in the Moon's largest impact crater.
Data from the Moon Mineralogy Mapper that flew aboard India's Chandrayaan-1 lunar orbiter shows a diverse mineralogy in the subsurface of the giant South Pole Aitken basin.
The differing mineral signatures could be reflective of the minerals dredged up at the time of the giant impact 4 billion years ago, ...
In power electronics systems bonded connections create the central electrical connections between adjoining surfaces.
The quality of these bonded connections is one of the main factors that determines the reliability and availability of drive systems in electric vehicles, and hence constitutes a major design challenge for German auto manufacturers aiming to electrify their vehicles.
Now the partners participating in the RoBE (Robust Bonds in ...
International team of scientists develops new feedback method for optimizing the laser pulse shapes used in the control of chemical reactions
In many ways, traditional chemical synthesis is similar to cooking. To alter the final product, you can change the ingredients or their ratio, change the method of mixing ingredients, or change the temperature or pressure of the environment of the ingredients.
Like an accomplished chef, chemists have become very skilled ...
11.12.2013 | Information Technology
11.12.2013 | Life Sciences
11.12.2013 | Agricultural and Forestry Science
11.12.2013 | Event News
10.12.2013 | Event News
05.12.2013 | Event News