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 Cancer cachexia: Extracellular ligand helps to prevent muscle loss
25.02.2020 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

nachricht The genetic secret of night vision
25.02.2020 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: High-pressure scientists in Bayreuth discover promising material for information technology

Researchers at the University of Bayreuth have discovered an unusual material: When cooled down to two degrees Celsius, its crystal structure and electronic properties change abruptly and significantly. In this new state, the distances between iron atoms can be tailored with the help of light beams. This opens up intriguing possibilities for application in the field of information technology. The scientists have presented their discovery in the journal "Angewandte Chemie - International Edition". The new findings are the result of close cooperation with partnering facilities in Augsburg, Dresden, Hamburg, and Moscow.

The material is an unusual form of iron oxide with the formula Fe₅O₆. The researchers produced it at a pressure of 15 gigapascals in a high-pressure laboratory...

Im Focus: From China to the South Pole: Joining forces to solve the neutrino mass puzzle

Study by Mainz physicists indicates that the next generation of neutrino experiments may well find the answer to one of the most pressing issues in neutrino physics

Among the most exciting challenges in modern physics is the identification of the neutrino mass ordering. Physicists from the Cluster of Excellence PRISMA+ at...

Im Focus: Therapies without drugs

Fraunhofer researchers are investigating the potential of microimplants to stimulate nerve cells and treat chronic conditions like asthma, diabetes, or Parkinson’s disease. Find out what makes this form of treatment so appealing and which challenges the researchers still have to master.

A study by the Robert Koch Institute has found that one in four women will suffer from weak bladders at some point in their lives. Treatments of this condition...

Im Focus: A step towards controlling spin-dependent petahertz electronics by material defects

The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.

Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

Turbomachine expander offers efficient, safe strategy for heating, cooling

25.02.2020 | Power and Electrical Engineering

The seismicity of Mars

25.02.2020 | Earth Sciences

Cancer cachexia: Extracellular ligand helps to prevent muscle loss

25.02.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>