Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mayo Clinic researchers use human antibody to cure malignant melanoma in mice

15.07.2004


Mayo Clinic researchers have manipulated a human antibody to induce an anti-tumor response in living mice that consistently curbs -- and often cures -- malignant melanoma, one of the most lethal forms of skin cancer and the most common cancer of young adults.


In the July 15 edition of Cancer Research Mayo researchers report three innovative discoveries that advance the emerging field of cancer immunotherapy. Cancer immunotherapy refers to scientist-controlled manipulations of the immune system to kill cancer cells without the toxic side effects of chemotherapy or radiation. These findings show that when administered intravenously, the human antibody can still induce immune response -- which suits it for potential therapeutic use as a drug for humans.

"What this current work demonstrates is that by using this antibody we can train the immune response to strike a new target," says Larry Pease, Ph.D., Mayo Clinic immunologist and lead investigator of the study.

The Discoveries



A novel way to fight cancer with the immune system

Treating live mice intravenously with a human antibody stimulates components of the immune system known as dendritic cells, which, in turn, changes the way dendritic cells interact with the T cells of the immune system. The result: a consistently strong -- and often curative -- treatment effect for malignant melanoma, a cancer that is newly diagnosed in approximately 51,000 people in the U.S. annually, and claims more than 7,000 lives a year in the United States.

New approach works to kill cancer in mice

The researchers created an anti-tumor immune response where none existed in nature. Under normal conditions dendritic cells are key players in initiating select immune responses -- responding to malignant melanoma just doesn’t happen to be among them. Mayo Clinic researchers changed that. They trained T cells to seek and destroy malignant melanoma by inducing activity of dendritic cells by "cross-linking" structures on their cell surface. Cross-linking is a molecular manipulation that can stimulate cells.

Effectiveness

In the investigation, one group of mice was treated intravenously with the experimental cross-linking antibody therapy, and two control groups were treated with known antibodies that do not prompt cross-linking structures containing B7-DC. All groups had malignant melanoma tumors transplanted into them. They were then examined 17 days later for evidence of tumor growth.

Results showed that in the two control groups, only one of 26 (less than 4 percent) were tumor free. By contrast, 11 of 16 mice -- 69 percent -- were tumor free in the group receiving the experimental antibody treatment. In addition, the few mice in this group that did develop tumors experienced significantly inhibited tumor growth compared to controls.

In a second line of investigation animals received intravenous transplants of tumors that seeded their lungs with dozens of discrete foci of melanoma, modeling what happens during lung metastasis. After three days, some of these animals were treated with the B7-DC cross-linking antibody or a control antibody. They were evaluated for tumor growth when their untreated counterparts had developed more than 50 tumor nodules in their lungs.

Forty-eight percent of the animals (14 of 29) that received B7-DC cross-linking antibody treatments were tumor free when the experiments were ended three to four weeks after tumor engraftment. In contrast, all the mice that received control antibodies developed large numbers of tumors in their lungs. Furthermore, all of the 52 percent of animals that developed melanoma lung nodules developed substantially fewer tumors relative to the animals receiving irrelevant antibody, showing that treatment with B7-DC cross-linking antibody had a strong treatment effect even when animals were not completely cured.

Distinct from previous methods

The data reveal a dramatic improvement in anti-tumor abilities of dendritic cells stimulated with this human antibody. Following treatment the dendritic cells behaved differently when compared to dendritic cells stimulated by established methods.

"Essentially, we are inducing an immune response against a tumor where an immune response isn’t normally happening," says Dr. Pease. "The human antibody induces strong tumor immunity when administered and without further interventions -- even after tumors are already established. This is an important milestone for any cancer therapy that will be useful for treating patients."

In addition to Dr. Pease, the coauthors of the article include: Suresh Radhakrishnan, Ph.D.; Loc Tan Nguyen; Bogoljub Ciric; Dallas Flies; Virginia P. Van Keulen; Koji Tamada; Lieping Chen and Moses Rodriguez, M.D. Their work was supported by grants from The Ralph C. Wilson, Sr., and Ralph C. Wilson, Jr., Medical Research Foundation, the Mayo Clinic Comprehensive Cancer Center and the National Cancer Institute of the National Institutes of Health.

Bob Nellis | EurekAlert!
Further information:
http://www.mayo.edu
http://cancerres.aacrjournals.org

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>