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

More articles from Health and Medicine:

nachricht One gene closer to regenerative therapy for muscular disorders
01.06.2017 | Cincinnati Children's Hospital Medical Center

nachricht The gut microbiota plays a key role in treatment with classic diabetes medication
01.06.2017 | University of Gothenburg

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: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>