Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Vaccine targets malignant brain cancer antigens, significantly lengthens survival

15.08.2012
An experimental immune-based therapy more than doubled median survival of patients diagnosed with the most aggressive malignant brain tumor, Cedars-Sinai Medical Center researchers reported in Cancer Immunology, Immunotherapy, published online Aug. 3.

Median survival in a Phase I clinical trial at Cedars-Sinai's Johnnie L. Cochran, Jr. Brain Tumor Center was 38.4 months, significantly longer than the typical 14.6-month survival of patients with newly diagnosed glioblastoma receiving standard therapy alone, which includes radiation and chemotherapy.

Median progression-free survival - the time from treatment to tumor recurrence - was 16.9 months, compared to the typical 6.9 months with standard care.

The study included 16 newly diagnosed patients who could be properly evaluated between May 2007 and January 2010. At later follow-up, six patients (38 percent) - ranging from 49 to 66 months post-treatment - showed no evidence of tumor recurrence and were free of disease without current active treatment. Eight patients remained alive.

"Brain tumors evade the immune system to survive, and the vaccine is intended to alert the immune system to the existence of cancer cells and activate a tumor-killing response. We also are targeting cells that we believe generate and perpetuate cancers," said Keith L. Black, MD, chair and professor of Cedars-Sinai's Department of Neurosurgery, director of the Cochran Brain Tumor Center and director of the Maxine Dunitz Neurosurgical Institute, where the vaccine was researched and developed. Black is the Ruth and Lawrence Harvey Chair in Neuroscience.

The vaccine's latest version, ICT-107, targets six antigens (HER2/neu, TRP-2, gp100, MAGE-1, IL13RĄ2 and AIM-2) involved in the development of glioblastoma cells. All patient tumors had at least three of the targeted antigens; 74 percent of tumors had all six. Patients with tumors that expressed large amounts of MAGE-1, AIM-2, gp100 and HER2 had better immune responses and longer progression-free survival rates, suggesting that these antigens may be particularly vulnerable to the vaccine.

The researchers also found evidence that the vaccine attacks some brain cancer stem cells, considered the original source of tumor cells. These self-renewing cells appear to enable tumors to resist radiation and chemotherapy and even regenerate after treatment. Cancer stem cells are especially appealing targets: killing the stem cells is believed to improve the chances of destroying a tumor and preventing its recurrence.

"The correlation of clinical responses to the level of antigen expression gives us confidence in our belief that a strong immunologic response is linked to clinical outcome. This finding supports our previous finding that immune responses are correlated to survival," commented John S. Yu, MD, vice chair of the Department of Neurosurgery, director of the Brain Tumor Center, professor of neurosurgery and senior author of the article.

Three of the tumor-associated antigens (HER2/neu, TRP-2 and AIM-2) are found not only on brain tumor cells but also on brain cancer stem cells, and the researchers reported that a protein (CD133) associated with cancer stem cells was decreased or eliminated from tumors of some vaccinated patients whose glioblastomas returned after treatment.

"Previous studies showed an increase in CD133 expression in patients who underwent treatment with radiation and chemotherapy. Our findings suggest that targeting antigens that are highly expressed by cancer stem cells may be a viable strategy for treating patients who have glioblastoma," said Surasak Phuphanich, MD, director of the Neuro-Oncology Program at the Cochran Brain Tumor Center and professor of neurology with Cedars-Sinai's Department of Neurosurgery and Department of Neurology.

Phuphanich and Christopher J. Wheeler, PhD, principal investigator in the Immunology Program at the Maxine Dunitz Neurosurgical Institute and associate professor of neurosurgery, are first authors of the article.

Cedars-Sinai's first dendritic cell vaccine began Phase I experimental treatments in May 1998. With the ability of the latest version, ICT-107, to stimulate a targeted and controlled immune response established in this Phase I study, the vaccine moved into a Phase II multicenter, randomized, placebo-controlled trial in 2011. Enrollment in the Phase II trial is expected to be completed in September 2012.

Dendritic cells are the immune system¡¦s most powerful antigen-presenting cells - those responsible for helping the immune system recognize invaders. They are derived from white blood cells taken from the patient in a routine blood draw. In the laboratory, the cells are cultured with synthetic peptides of the six antigens - essentially training the dendritic cells to recognize the tumor antigens as targets.

When the "new" dendritic cells in the vaccine are injected under the patient's skin in the armpit, they are intended to seek and destroy lingering tumor cells. Vaccine is administered three times at two-week intervals after standard radiation and chemotherapy.

ICT-107 is a product of the biotechnology company ImmunoCellular Therapeutics, Ltd. Keith L. Black, MD, chair of Cedars-Sinai's Department of Neurosurgery, director of the Maxine Dunitz Neurosurgical Institute, director of the Johnnie L. Cochran, Jr. Brain Tumor Center and the Ruth and Lawrence Harvey Chair in Neuroscience, is chairman of the company's scientific advisory board. John S. Yu, MD, vice chair of the Department of Neurosurgery, director of the Brain Tumor Center, director of Surgical Neuro-Oncology and surgical director of the Gamma Knife Center at Cedars-Sinai, is chief scientific officer and chairman of the board. Yu and another author are salaried employees of the company and own stock in it; Black and another author are consultants for the company and stock owners. Certain rights in the dendritic cell vaccine technology and corresponding intellectual property have been exclusively licensed by Cedars-Sinai to ImmunoCellular Therapeutics, including subsequently developed versions of the vaccine investigated in this clinical study. Cedars-Sinai also owns stock in the company.

Citation: Cancer Immunology, Immunotherapy, "Phase I trial of a multi-epitope pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma," online Aug. 3, 2012.

Sandy Van | Cedars-Sinai News
Further information:
http://www.cedars-sinai.edu

More articles from Studies and Analyses:

nachricht The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig

nachricht Win-win strategies for climate and food security
02.10.2017 | International Institute for Applied Systems Analysis (IIASA)

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Corporate coworking as a driver of innovation

22.11.2017 | Business and Finance

PPPL scientists deliver new high-resolution diagnostic to national laser facility

22.11.2017 | Physics and Astronomy

Quantum optics allows us to abandon expensive lasers in spectroscopy

22.11.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>