Animal experiments show that it is relatively easy to treat cancer in the early stages. However, it is far more difficult to successfully treat advanced cancer. Treatment of brain tumors is particularly challenging because regulatory T-cells accumulate in brain tumors and suppress an immune attack.
In several steps using a new strategy and a novel drug, Burkhard Becher's team from the Institute of Experimental Immunology at the University of Zurich has now succeeded in doing exactly this in the case of glioblastoma, one of the most dangerous brain tumors. First step, they stimulated the body's own immune system in such a way that it recognised and then killed the brain tumor cells even in advanced stages of the disease.
The initial objective of their new study was to break through the tumor's protective shield. "We wanted to establish whether we can actually elicit an immune response to a tumor growing within the brain", explains Burkhard Becher. To this end, the team used the immune messenger substance, Interleukin-12. When Interleukin-12 is produced in the tumor, immune cells are stimulated locally in such a manner that the tumor is attacked and rejected. Once this procedure had worked well in the early stages of the tumor, the researchers waited in the next stage until the tumor was very large and the life expectancy of the untreated test animals was less than three weeks. "We only began treatment when it was, in fact, already too late", says the first author of the study Johannes vom Berg. The success rate was low, Berg adds. "We then injected biopharmaceutical Interleukin-12 into the large brain tumor. This did induce an immune response but only led to tumor rejection in one-quarter of the animals."
From 25 to 80 percent: combined treatment leads to success
The researchers were successful when they drew on a new development in skin cancer treatment. They combined intra-tumoral Interleukin-12 treatment with the intravenous administration of a novel immunostimulating drug that suppresses the regulatory T-cells. The rejection of the tumor then worked in 80 percent of the test animals. "I have rarely seen such convincing data in preclinical glioma treatment", says Michael Weller, neurooncologist and Director of the Clinic for Neurology at the University Hospital Zurich. He added, "That's why this development should be tested as soon as possible in clinical trials."
In a joint trial, the team then tested the treatment in a further tumor model which mimics the clinical situation of the brain tumor patient even better. And once again they were successful.
The next step: a clinical trial as soon as possible
The findings of the current research work have been published in the Journal of Experimental Medicine. Their promising results do not mean that the treatment can already be as effective in brain tumor patients. This has to be examined in the next phase for which the team now actively seek commercial partners. Burkhard Becher puts it like this, "We are cautiously optimistic but it's time that we adopted completely new strategies to really get to grips with this fatal tumor"
Explore further: Nano drug crosses blood-brain tumor barrier, targets brain tumor cells and blood vessels
More information: Johannes vom Berg, Melissa Vrohlings, Sergio Haller, Aladin Haimovici, Paulina Kulig, Anna Sledzinska, Michael Weller and Burkhard Becher. Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell mediated glioma rejection. The Journal of Experimental Medicine (JEM). November 25, 2013.DOI: 10.1084/jem.20130678
Medical Xpress on facebook
Related Stories
Nano drug crosses blood-brain tumor barrier, targets brain tumor cells and blood vessels
Jul 17, 2013
(Phys.org) —An experimental drug in early development for aggressive brain tumors can cross the blood-brain tumor barrier and kill tumor cells and block the growth of tumor blood vessels, according to a recent study led ...
Poliovirus vaccine trial shows early promise for recurrent glioblastoma
May 21, 2013
An attack on glioblastoma brain tumor cells that uses a modified poliovirus is showing encouraging results in an early study to establish the proper dose level, researchers at Duke Cancer Institute report.
Pitt team aims to change tissue microenvironment to fend off cancerous tumors
Nov 15, 2013
The magic to killing cancer cells might not be in the bullet, but in the gunpowder that accompanies it, according to researchers at the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter. Instead ...
50 percent of patients in Cedars-Sinai brain cancer study alive after five years
Nov 24, 2013
Eight of 16 patients participating in a study of an experimental immune system therapy directed against the most aggressive malignant brain tumors – glioblastoma multiforme – survived longer than five years after diagnosis, ...
UC Irvine opens clinical trial of novel treatment for brain cancer
Oct 10, 2012
UC Irvine doctors are enrolling patients with the deadly brain tumor glioblastoma multiforme in a clinical trial of a vaccine that may prevent the cancer's return or spread after surgery.
Recommended for you
Severe flu complications for cancer patients
1 hour ago
It is often noted that very young people and the elderly are most at-risk for experiencing flu-related complications, and one expert at the University of Alabama at Birmingham says people with weakened immune ...
Do aging cells become cancer?
1 hour ago
Cancers that occur in later life could be down to the way our cells age, according to a paper published in Nature Cell Biology.
Potential new treatments for acute myeloid leukemia
1 hour ago
Two separate studies yield key findings for the prevention, diagnosis, treatment and cure for acute myeloid leukemia (AML). AML is a group of heterogeneous diseases with considerable diversity in terms of genetic abnormalities. ...
A better pump for pediatric brain cancer
2 hours ago
Treating pediatric brain cancer can be a challenge, since the brain has ways to protect itself from drugs taken orally or intravenously. One solution to this frustrating problem: A miniature, implantable ...
Certain symptom clusters experienced after surgery for esophageal cancer predict poor prognosis
10 hours ago
A new study has found that several months after surgery for esophageal cancer, different symptoms cluster together in different types of patients. In addition, patients with certain symptom clusters have an increased risk ...
Nexavar approval expanded for common thyroid cancer
23 hours ago
(HealthDay)—U.S. Food and Drug Administration approval for the anti-cancer drug Nexavar (sorafenib) has been expanded to include late-stage differentiated thyroid cancer, the most common type of thyroid ...
User comments
© Medical Xpress 2011-2013, Phys.org network
Animal experiments show that it is relatively easy to treat cancer in the early stages. However, it is far more difficult to successfully treat advanced cancer. Treatment of brain tumors is particularly challenging because regulatory T-cells accumulate in brain tumors and suppress an immune attack.
In several steps using a new strategy and a novel drug, Burkhard Becher's team from the Institute of Experimental Immunology at the University of Zurich has now succeeded in doing exactly this in the case of glioblastoma, one of the most dangerous brain tumors. First step, they stimulated the body's own immune system in such a way that it recognised and then killed the brain tumor cells even in advanced stages of the disease.
The initial objective of their new study was to break through the tumor's protective shield. "We wanted to establish whether we can actually elicit an immune response to a tumor growing within the brain", explains Burkhard Becher. To this end, the team used the immune messenger substance, Interleukin-12. When Interleukin-12 is produced in the tumor, immune cells are stimulated locally in such a manner that the tumor is attacked and rejected. Once this procedure had worked well in the early stages of the tumor, the researchers waited in the next stage until the tumor was very large and the life expectancy of the untreated test animals was less than three weeks. "We only began treatment when it was, in fact, already too late", says the first author of the study Johannes vom Berg. The success rate was low, Berg adds. "We then injected biopharmaceutical Interleukin-12 into the large brain tumor. This did induce an immune response but only led to tumor rejection in one-quarter of the animals."
From 25 to 80 percent: combined treatment leads to success
The researchers were successful when they drew on a new development in skin cancer treatment. They combined intra-tumoral Interleukin-12 treatment with the intravenous administration of a novel immunostimulating drug that suppresses the regulatory T-cells. The rejection of the tumor then worked in 80 percent of the test animals. "I have rarely seen such convincing data in preclinical glioma treatment", says Michael Weller, neurooncologist and Director of the Clinic for Neurology at the University Hospital Zurich. He added, "That's why this development should be tested as soon as possible in clinical trials."
In a joint trial, the team then tested the treatment in a further tumor model which mimics the clinical situation of the brain tumor patient even better. And once again they were successful.
The next step: a clinical trial as soon as possible
The findings of the current research work have been published in the Journal of Experimental Medicine. Their promising results do not mean that the treatment can already be as effective in brain tumor patients. This has to be examined in the next phase for which the team now actively seek commercial partners. Burkhard Becher puts it like this, "We are cautiously optimistic but it's time that we adopted completely new strategies to really get to grips with this fatal tumor"
Explore further: Nano drug crosses blood-brain tumor barrier, targets brain tumor cells and blood vessels
More information: Johannes vom Berg, Melissa Vrohlings, Sergio Haller, Aladin Haimovici, Paulina Kulig, Anna Sledzinska, Michael Weller and Burkhard Becher. Intratumoral IL-12 combined with CTLA-4 blockade elicits T cell mediated glioma rejection. The Journal of Experimental Medicine (JEM). November 25, 2013.DOI: 10.1084/jem.20130678
Medical Xpress on facebook
Related Stories
Nano drug crosses blood-brain tumor barrier, targets brain tumor cells and blood vessels
Jul 17, 2013
(Phys.org) —An experimental drug in early development for aggressive brain tumors can cross the blood-brain tumor barrier and kill tumor cells and block the growth of tumor blood vessels, according to a recent study led ...
Poliovirus vaccine trial shows early promise for recurrent glioblastoma
May 21, 2013
An attack on glioblastoma brain tumor cells that uses a modified poliovirus is showing encouraging results in an early study to establish the proper dose level, researchers at Duke Cancer Institute report.
Pitt team aims to change tissue microenvironment to fend off cancerous tumors
Nov 15, 2013
The magic to killing cancer cells might not be in the bullet, but in the gunpowder that accompanies it, according to researchers at the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter. Instead ...
50 percent of patients in Cedars-Sinai brain cancer study alive after five years
Nov 24, 2013
Eight of 16 patients participating in a study of an experimental immune system therapy directed against the most aggressive malignant brain tumors – glioblastoma multiforme – survived longer than five years after diagnosis, ...
UC Irvine opens clinical trial of novel treatment for brain cancer
Oct 10, 2012
UC Irvine doctors are enrolling patients with the deadly brain tumor glioblastoma multiforme in a clinical trial of a vaccine that may prevent the cancer's return or spread after surgery.
Recommended for you
Severe flu complications for cancer patients
1 hour ago
It is often noted that very young people and the elderly are most at-risk for experiencing flu-related complications, and one expert at the University of Alabama at Birmingham says people with weakened immune ...
Do aging cells become cancer?
1 hour ago
Cancers that occur in later life could be down to the way our cells age, according to a paper published in Nature Cell Biology.
Potential new treatments for acute myeloid leukemia
1 hour ago
Two separate studies yield key findings for the prevention, diagnosis, treatment and cure for acute myeloid leukemia (AML). AML is a group of heterogeneous diseases with considerable diversity in terms of genetic abnormalities. ...
A better pump for pediatric brain cancer
2 hours ago
Treating pediatric brain cancer can be a challenge, since the brain has ways to protect itself from drugs taken orally or intravenously. One solution to this frustrating problem: A miniature, implantable ...
Certain symptom clusters experienced after surgery for esophageal cancer predict poor prognosis
10 hours ago
A new study has found that several months after surgery for esophageal cancer, different symptoms cluster together in different types of patients. In addition, patients with certain symptom clusters have an increased risk ...
Nexavar approval expanded for common thyroid cancer
23 hours ago
(HealthDay)—U.S. Food and Drug Administration approval for the anti-cancer drug Nexavar (sorafenib) has been expanded to include late-stage differentiated thyroid cancer, the most common type of thyroid ...
User comments
© Medical Xpress 2011-2013, Phys.org network
No comments:
Post a Comment