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 Improving memory with magnets
28.03.2017 | McGill University

nachricht Graphene-based neural probes probe brain activity in high resolution
28.03.2017 | Graphene Flagship

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: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>