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 New study first to predict which oil and gas wells are leaking methane
21.12.2018 | University of Vermont

nachricht Droughts boost emissions as hydropower dries up
21.12.2018 | Stanford's School of Earth, Energy & Environmental Sciences

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: Ten-year anniversary of the Neumayer Station III

The scientific and political community alike stress the importance of German Antarctic research

Joint Press Release from the BMBF and AWI

The Antarctic is a frigid continent south of the Antarctic Circle, where researchers are the only inhabitants. Despite the hostile conditions, here the Alfred...

Im Focus: Ultra ultrasound to transform new tech

World first experiments on sensor that may revolutionise everything from medical devices to unmanned vehicles

The new sensor - capable of detecting vibrations of living cells - may revolutionise everything from medical devices to unmanned vehicles.

Im Focus: Flying Optical Cats for Quantum Communication

Dead and alive at the same time? Researchers at the Max Planck Institute of Quantum Optics have implemented Erwin Schrödinger’s paradoxical gedanken experiment employing an entangled atom-light state.

In 1935 Erwin Schrödinger formulated a thought experiment designed to capture the paradoxical nature of quantum physics. The crucial element of this gedanken...

Im Focus: Nanocellulose for novel implants: Ears from the 3D-printer

Cellulose obtained from wood has amazing material properties. Empa researchers are now equipping the biodegradable material with additional functionalities to produce implants for cartilage diseases using 3D printing.

It all starts with an ear. Empa researcher Michael Hausmann removes the object shaped like a human ear from the 3D printer and explains:

Im Focus: Elucidating the Atomic Mechanism of Superlubricity

The phenomenon of so-called superlubricity is known, but so far the explanation at the atomic level has been missing: for example, how does extremely low friction occur in bearings? Researchers from the Fraunhofer Institutes IWM and IWS jointly deciphered a universal mechanism of superlubricity for certain diamond-like carbon layers in combination with organic lubricants. Based on this knowledge, it is now possible to formulate design rules for supra lubricating layer-lubricant combinations. The results are presented in an article in Nature Communications, volume 10.

One of the most important prerequisites for sustainable and environmentally friendly mobility is minimizing friction. Research and industry have been dedicated...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Our digital society in 2040

16.01.2019 | Event News

11th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Aachen, 3-4 April 2019

14.01.2019 | Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

 
Latest News

Additive manufacturing reflects fundamental metallurgical principles to create materials

18.01.2019 | Materials Sciences

How molecules teeter in a laser field

18.01.2019 | Life Sciences

The cytoskeleton of neurons has been found to be involved in Alzheimer's disease

18.01.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>