Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Antigen Targeted In Therapy for Melanoma also Prompts Immune Response in Brain Tumor Cells

25.09.2003


A protein fragment that was previously found in melanomas has now been detected in highly aggressive brain tumors called gliomas that take the lives of about 15,000 Americans each year.

This peptide, which the immune system recognizes as an antigen, or foreign invader, appears to be a target for anti-tumor immune therapy, according to studies conducted by researchers at Cedars-Sinai’s Maxine Dunitz Neurosurgical Institute and the National Cancer Institute. It also may be useful as a marker that will enable scientists to monitor immune responses in human clinical trials against cancer cells called glioblastoma multiforme (GBM), often referred to as gliomas.

Institute scientists and neurosurgeons have for several years conducted clinical trials using immunotherapy techniques to battle gliomas, removing brain tumor cells and culturing them with immune system cells called dendritic cells in the lab. When the resulting "vaccine" is injected into the patient’s bloodstream, the dendritic cells recognize the tumor cells as invaders and "present" them to the antigen-fighting T-lymphocytes, triggering an immune response.



"The outlook for patients who suffer from these highly aggressive tumors has historically been extremely poor, and even conventional treatments such as surgery, chemotherapy and radiation therapy have provided almost no benefit," said Keith L. Black, M.D., neurosurgeon and founder and director of the Institute. "Based on the results of our early studies, the immune system appears to have the potential to destroy glioma cells and contribute to longer periods of patient survival. Unfortunately, the immune system is not very effective on its own. Therefore, we are always looking for new ways to target and boost the immune response."

In mouse and human studies of melanoma, tyrosinase-related protein-2 (TRP-2) has proved to be an excellent target for immunotherapies. This study found that the TRP-2 antigen also was expressed at significant levels in glioma cells and that a strong immune response could be triggered against it.

Tests were conducted on the genetic material of established glioma cell lines and on cells of brain tumors removed from patients undergoing treatment at the Maxine Dunitz Neurosurgical Institute. Lab results demonstrated that TRP-2 protein was expressed in primary cultured glioma cells and in fresh tissue.

Additional tests found that certain cytotoxic T lymphocytes - immune system cells that attack invaders - were able to recognize TRP-2 as a target when TRP-2 was expressed in significant levels. The degree of recognition correlated with the level of TRP-2 expression in the genetic material, an important finding because TRP-2 is expressed to lesser degrees - below the recognition and immune activation threshold - in normal brain tissue.

The researchers also were able to generate in the laboratory an immune response using blood cells and dendritic cells from a healthy donor and specially prepared TRP-2-positive glioma cells. The immune cells were able to recognize the TRP-2 positive GBM tumor cell lines, and an increase in TRP-2-specific antigen-killing activity could be seen. The identification of TRP-2 as a brain tumor-associated antigen appears, therefore, to offer not only a new target for immunotherapy, but a way to monitor related immune responses.

An increase in TRP-2-related immune activity also was detected in four patients with malignant brain tumors who were part of a clinical trial at the Maxine Dunitz Neurosurgical Institute. Cytotoxic T lymphocyte activity was significantly increased after three dendritic cell vaccinations, and the patients appeared to have no adverse effects from the vaccinations.

Research scientist Gentao Liu, Ph.D., was the paper’s first author. Other Institute contributors included research scientist Christopher J. Wheeler, Ph.D.; John S. Yu, M.D., co-director of the Comprehensive Brain Tumor Program; Dr. Black, who directs the medical center’s Division of Neurosurgery and the Comprehensive Brain Tumor Program and holds the Ruth and Lawrence Harvey Chair in Neuroscience; and research scientist Han Ying, Ph.D. Hung T. Khong, M.D., a contributing author from the Surgery Branch of the National Cancer Institute, was involved in previous discoveries of TRP-2 in melanoma.

Funding was provided in part by National Institutes of Health grant NS02232-01 to Dr. Yu.

Cedars-Sinai is one of the largest nonprofit academic medical centers in the Western United States. For the fifth straight two-year period, it has been named Southern California’s gold standard in health care in an independent survey. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities and its broad spectrum of programs and services, as well as breakthroughs in biomedical research and superlative medical education. Named one of the 100 "Most Wired" hospitals, the Medical Center ranks among the top 10 non-university hospitals in the nation for its research activities.

Sandy Van | Van Communications

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Nonstop Tranport of Cargo in Nanomachines

Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.

Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

Nonstop Tranport of Cargo in Nanomachines

20.11.2018 | Life Sciences

Researchers find social cultures in chimpanzees

20.11.2018 | Life Sciences

When AI and optoelectronics meet: Researchers take control of light properties

20.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>