Johns Hopkins researchers say they have found a specific protein in nearly 100 percent of high-grade meningiomas -- the most common form of brain tumor -- suggesting a new target for therapies for a cancer that does not respond to current chemotherapy.
Importantly, the investigators say, the protein -- NY-ESO-1 -- is already at the center of a clinical trial underway at the National Cancer Institute. That trial is designed to activate the immune systems of patients with other types of tumors that express the protein, training the body to attack the cancer and eradicate it.
"Typically there is a lag time before a laboratory finding like this leads to a clear path forward to help patients. But in this case, since there is already a clinical trial underway, we have a chance of helping people sooner rather than later," says Gregory J. Riggins, M.D., Ph.D., a professor of neurosurgery at the Johns Hopkins University School of Medicine and the senior author of the study published online in the journal Cancer Immunology Research.
In the NCI trial, NY-ESO-1 is found in a much smaller percentage of tumors than Riggins and his team found in high-grade meningioma, suggesting that for the brain cancer, the target would be potentially more significant.
Most low-grade meningiomas located in easy-to-reach locations can be treated successfully with surgery and radiation. But more atypical, higher-grade tumors are much more difficult to eradicate and are deadlier.
Riggins and his colleagues, including Gilson S. Baia, Ph.D., and Otavia L. Caballero, M.D., Ph.D., set out to find cancer antigens in meningioma. Cancer antigens are proteins expressed in tumors but not in healthy cells, making them good targets for chemical or immune system attack. They looked specifically at 37 cancer/testis (CT) genes, which are not found in normal cells in the body except in germ cells and cells cordoned off in the testicles or, in some cases, ovaries.
CT genes are activated, however, in various cancers. While they are seen as "foreign" by the body's immune system, they are often locked behind the sophisticated defense system that cancers use to evade attack by immune cells. Finding a way to get the immune system to see these protein antigens, however, could allow for the body to recognize the invasion and go after the cancer cells. Various approaches are being used to do that, including vaccines and a system involving removing T-cells from the body and reprogramming them before returning them and setting them loose on the cancer cells.
The Johns Hopkins researchers took tissue from 18 different meningioma samples, removed the genetic material and protein and checked at what levels the 37 different genes were turned on. The gene that is the blueprint for the NY-ESO-1 protein was turned on more frequently than any other, in five of the 18 patient samples.
Then they analyzed NY-ESO-1 expression in a larger group of 110 meningioma tissue samples. They found NY-ESO-1 in 108 of them. The more expression in the sample, they also determined, the higher the tumor grade. The higher levels of NY-ESO-1 expressed also correlated with significantly lower disease-free and overall survival rates in the patients they came from.
The NCI trial originally began in melanoma patients. NY-ESO-1 is expressed in roughly one-third of melanomas as well as approximately one-third of breast, prostate, lung, ovarian, thyroid and bladder cancers, as well as sarcomas. Riggins and his team did not find the protein in glioblastoma, the deadliest form of brain cancer.
He calls the fact that the NCI trial could now include meningioma patients a "stroke of luck."
"If that therapy did not exist, there would be a lot of work that would have to be done to convince people to pursue this," Riggins says. "Our goal is to get something that works to the patients. This puts us well on our way."
Other Johns Hopkins researchers involved in the study include Qi Zhao, Ph.D.; Zev A. Binder, M.D.; Gary L. Gallia, M.D.; Alfredo Quiñones-Hinojosa, M.D.; Alessandro Olivi, M.D.; Henry Brem, M.D.; Peter Burger, M.D.; Robert L. Strausberg, Ph.D.; and Charles Eberhart, M.D., Ph.D.
The research was funded by the Virginia and D. K. Ludwig Fund for Cancer Research, the Ludwig Institute for Cancer Research, Meningioma Mommas, Margaret H. Riggins, Leonard and Phyllis Attman, and the Irving J. Sherman Research Professorship.
For more information about the Riggins lab:
Johns Hopkins Medicine
Johns Hopkins Medicine (JHM), headquartered in Baltimore, Maryland, is a $6.5 billion integrated global health enterprise and one of the leading health care systems in the United States. JHM unites physicians and scientists of the Johns Hopkins University School of Medicine with the organizations, health professionals and facilities of the Johns Hopkins Hospital and Health System. JHM's mission is to improve the health of the community and the world by setting the standard of excellence in medical education, research and clinical care. Diverse and inclusive, JHM educates medical students, scientists, health care professionals and the public; conducts biomedical research; and provides patient-centered medicine to prevent, diagnose and treat human illness. JHM operates six academic and community hospitals, four suburban health care and surgery centers, and more than 30 primary health care outpatient sites. The Johns Hopkins Hospital, opened in 1889, was ranked number one in the nation from 1990 to 2011 by U.S. News & World Report.
Stephanie Desmon | EurekAlert!
Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign
Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences