Cocktail boosts immune cells in fighting cancer

December 06, 2012

Fighting cancer using the body's own defense system is a promising treatment approach. Immune therapies have even become clinical routine in treating a few 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," 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.
-end-
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.

Helmholtz Association

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.