Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Immune vaccine followed by chemotherapy slows incurable brain tumors, lengthens survival

16.08.2004


Researchers at Cedars-Sinai’s Maxine Dunitz Neurosurgical Institute have found that the combination of immunotherapy and chemotherapy significantly slowed tumor progression and extended survival of patients with glioblastoma multiforme (GBM), extremely aggressive and incurable brain tumors.

Although the exact mechanism is yet to be identified, the research team theorizes that like a one-two punch, the anti-tumor vaccine delivers an initial blow to the tumor cells which increases their vulnerability to tumor-killing drugs.

In an article published in the August 15, 2004 Clinical Cancer Research, the scientists say these "results suggest that chemotherapy synergizes with previous therapeutic vaccination to generate a uniquely effective treatment that slows GBM progression and significantly extends patient survival relative to individual therapies."



The average length of survival was extended to about 26 months when patients received the combined therapies, compared to 18 months for those who received vaccine alone and 16 months for those undergoing chemotherapy alone.

Five of 12 patients (41.7 percent) who received vaccine and chemotherapy survived past the two-year point, compared with only one of 12 (8.3 percent) who received the vaccine alone and one of 12 who received chemotherapy alone. Also, two patients who underwent combined therapy lived past the three-year mark while no patients receiving either single therapy survived this long.

"We’re very excited about the results. Obviously they need to be confirmed in a randomized trial, but assuming these outcomes are reproducible, it would be extremely gratifying to see this kind of increase in survival for such a devastating disease," said Keith L. Black, MD, Institute director and one of five Institute researchers who authored the paper.

Patients ranged in age from 32 to 78 years, with an average of 55 years. All of those whose cases were reviewed had first undergone tumor-removal surgery and radiation therapy. One group then received chemotherapy alone, another received vaccine alone and a third group was treated with vaccine followed by chemotherapy. Those who received vaccine, either alone or in combination, were participants in dendritic-cell vaccine studies conducted between 1998 and 2001 at the Institute.

Pioneered at Cedars-Sinai in the treatment of GBM, dendritic cell immunotherapy introduces foreign proteins from surgically removed tumors to "dendritic" cells taken from a patient’s blood. Dendritic cells, also called antigen-presenting cells, are elements of the immune system that "present" foreign material to cell-killing T lymphocytes.

In the laboratory, the tumor cells are cultured with the dendritic cells to enable the immune cells to recognize cancer cells as targets for attack. When the "new," specialized dendritic cells are injected back into the patient, they seek out remaining tumor cells and signal for T lymphocytes to destroy them.

In this study, all patients in the immunotherapy groups received three vaccines at two-week intervals. Patients in one of the clinical trials received a fourth injection six weeks later. All patients underwent magnetic resonance imaging to monitor their progress every two to three months.

Although several studies in the laboratory and in human tissue have documented the cancer-tracking and attacking abilities of dendritic cells and T lymphocytes, actual patient survival rates have remained virtually unchanged, perhaps because the tumor-killing action of T lymphocytes cannot keep pace with tumor cells that rapidly multiply and mutate.

"We know from our ongoing studies that the vaccine is able to elicit a strong anti-tumor response, but it appears that these extremely malignant tumors are inherently resistant to vaccine-elicited immune destruction alone," explained Christopher J. Wheeler, PhD, research scientist who is the paper’s first author.

"The fact that tumors treated with dendritic cell therapy are highly sensitive to subsequent chemotherapy suggests that the vaccine either ’primes’ the cell-death machinery or fundamentally alters the genetic or structural makeup of the tumor cells. Based on these results, it appears that this weakness can be exploited by the follow-up administration of drugs that attack the tumor’s DNA."

Asha Das, MD, who directs the Institute’s Neuro-oncology Program and has extensive clinical and research experience, said the benefits of combined therapy appear to markedly surpass those seen in previous vaccine studies and even the most optimistic analyses of chemotherapy in the treatment of GBM. "This is the first demonstration that a vaccine-based therapy followed by chemotherapy can provide clinical improvement to a majority of treated cancer patients," she said.

The authors went on to show that chemotherapeutic responsiveness in all vaccinated GBM patients was most strongly correlated with the size of a particular population of newly produced immune cells thought to be especially important for anti-GBM immune responses. "Despite the limitations associated with a non-randomized study, this constitutes evidence favoring the hypothesis that anti-tumor immunity impacts GBM chemosensitivity. Based on these results, we are developing a randomized Phase III trial with other institutions to confirm whether dendritic cell vaccination followed by chemotherapy will prolong survival in patients with glioblastoma," said John S. Yu, MD, who directs the Institute’s Stereotactic Radiosurgery Program, oversees clinical vaccine administration, and serves as co-director of the Comprehensive Brain Tumor Program. He and Gentao Liu, PhD, contributed immune cytotoxicity analysis for the report.

Seeing such positive results against a cancer as virulent as GBM, the Cedars-Sinai researchers anticipate that similar vaccine-drug combinations may prove to be at least as effective against other types of cancers. Assuming that follow-up studies support these early findings, the dendritic vaccine-chemotherapy approach may quickly become the treatment of choice for GBM patients while the search continues for even more effective treatments.

"Until now, there has been very little in terms of therapy that makes a difference for this type of disease. What we’re seeing here for the first time is what appears to be a significant increase in survival," said Dr. Black, who founded the Maxine Dunitz Neurosurgical Institute in 1997, directs Cedars-Sinai’s Division of Neurosurgery and the Comprehensive Brain Tumor Program, and holds the Ruth and Lawrence Harvey Chair in Neuroscience.

Sandra Van | EurekAlert!
Further information:
http://www.csmc.edu

More articles from Health and Medicine:

nachricht Routing gene therapy directly into the brain
07.12.2017 | Boston Children's Hospital

nachricht New Hope for Cancer Therapies: Targeted Monitoring may help Improve Tumor Treatment
01.12.2017 | Berliner Institut für Gesundheitsforschung / Berlin Institute of Health (BIH)

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: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

Im Focus: Virtual Reality for Bacteria

An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications

Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...

Im Focus: A space-time sensor for light-matter interactions

Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.

The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...

Im Focus: A transistor of graphene nanoribbons

Transistors based on carbon nanostructures: what sounds like a futuristic dream could be reality in just a few years' time. An international research team working with Empa has now succeeded in producing nanotransistors from graphene ribbons that are only a few atoms wide, as reported in the current issue of the trade journal "Nature Communications."

Graphene ribbons that are only a few atoms wide, so-called graphene nanoribbons, have special electrical properties that make them promising candidates for the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

Blockchain is becoming more important in the energy market

05.12.2017 | Event News

 
Latest News

Making fuel out of thick air

08.12.2017 | Life Sciences

Rules for superconductivity mirrored in 'excitonic insulator'

08.12.2017 | Information Technology

Smartphone case offers blood glucose monitoring on the go

08.12.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>