Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Triple therapy revs up immune system against common brain tumor

05.08.2014

A triple therapy for glioblastoma, including two types of immunotherapy and targeted radiation, has significantly prolonged the survival of mice with these brain cancers, according to a new report by scientists at the Johns Hopkins Kimmel Cancer Center.

Mice with implanted, mouse-derived glioblastoma cells lived an average of 67 days after the triple therapy, compared with mice that lasted 24 days when they received only the two immunotherapies. Half of the mice who received the triple therapy lived 100 days or more and were protected against further tumors when new cancer cells were re-injected under the animals' skins.

The combination treatment described in the July 11 issue of PLOS One consists of highly focused radiation therapy targeted specifically to the tumor and strategies that lift the brakes and activate the body's immune system, allowing anti-cancer drugs to attack the tumor. One of the immunotherapies is an antibody that binds to and blocks an immune checkpoint molecule on T cells called CTLA-4, allowing the T-cells to infiltrate and fight tumor cells. The second immunotherapy, known as 4-1BB, supplies a positive "go" signal, stimulating anti-tumor T cells.

None of the treatments are new, but were used by the Johns Hopkins team to demonstrate the value of combining treatments that augment the immune response against glioblastomas, the most common brain tumors in human adults. The prognosis is generally poor, even with early treatment.

"We're trying to find that optimal balance between pushing and pulling the immune system to kill cancer," said Charles Drake, M.D., Ph.D., an associate professor of oncology, immunology and urology, and medical oncologist at the Johns Hopkins Kimmel Cancer Center.

The researchers speculate that when radiation destroys tumor cells, the dead tumor cells may release proteins that help train immune cells to recognize and attack the cancer, said Michael Lim, M.D., an associate professor of neurosurgery, oncology at the Johns Hopkins University School of Medicine and member of Johns Hopkins' Institute of NanoBiotechnology.

"Traditionally, radiation is used as a definitive therapy to directly kill cancer cells," said Lim, who also serves as director of the Brain Tumor Immunotherapy Program and director of the Metastatic Brain Tumor Center at Johns Hopkins Medicine. "But in this situation we're using radiation as kind of kindling, to try to induce an immune response."

Lim says if further studies affirm the value of the triple therapy in animals and humans, the radiation could be delivered a few days before or after the immunotherapies and still achieve the same results. Lim said this leeway "could make applications of this therapy in patients possible."

The researchers say they were also encouraged to see that the triple therapy created "immune memory" in mice that were long-term survivors. When brain tumor cells were re-introduced under the skin of the animals, their immune systems appeared to protect them against the development of a new brain tumor.

Drake said since the immune system usually doesn't generate a memory when foreign (tumor) cells are still present in the body. "But the idea that this combination treatment was successful at generating immunological memory really suggests that we could do this in patients and generate some long-term responses."

The researchers are developing a variety of clinical trials to test combination therapies against brain tumors.

###

Other researchers on the study include Zineb Belcaid, Jillian A. Phallen, Alfred P. See, Dimitrios Mathios, Chelsea Gottschalk, Sarah Nicholas, Meghan Kellett, Jacob Ruzevick, Christopher Jackson, Xiaobu Ye, Betty Tyler, and Henry Brem of the Department of Neurosurgery at Johns Hopkins University School of Medicine; Jing Zeng, Phuoc T. Tran, and John W. Wong of the Department of Radiation Oncology and Molecular Radiation Sciences at the Johns Hopkins Kimmel Cancer Center; and Emilia Albesiano, Nicholas M. Durham, and Drew M. Pardoll at the Kimmel Center's Department of Oncology and Medicine, Division of Immunology.

Funding for the study was provided by the WW Smith Charitable Foundation and individual patient donations.

Michael Lim is a consultant for Accuray and receives research funding from Accuray, Bristol-Meyers Squibb, Celldex and Aegenus. Charles Drake has served as a consultant for Amplimmune, Bristol-Meyers Squibb, Compugen, Dendreon, ImmunExcite and Roche/Genentech and is on the Scientific Advisory Board of Compugen. He receives research funding from Bristol-Meyers Squibb, Aduro and Janssen and has stock ownership in Compugen. Drew Pardoll is a consultant/advisor for Jounce Therapeutics, Bristol-Meyers Squibb, ImmuneXcite and Aduro and receives research funding from Bristol-Meyers Squibb. Jing Zeng, Michael Lim, Charles Drake and Drew Pardoll hold a patent for the work related to this study. The authors declare that they have a patent relating to material pertinent to this article; this international patent application (PCT/US2012/043124) is entitled "Use of Adjuvant Focused Radiation Including Stereotactic Radiosurgery for Augmenting Immune Based Therapies Against Neoplasms." These relationships are being managed by The Johns Hopkins University in accordance with its conflict of interest policies.

On the Web:

PLOS One: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0101764

Johns Hopkins Medicine (JHM), headquartered in Baltimore, Maryland, is a $6.7 billion integrated global health enterprise and one of the leading academic 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 vision, "Together, we will deliver the promise of medicine," is supported by its mission 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 35 Johns Hopkins Community Physicians sites. The Johns Hopkins Hospital, opened in 1889, has been ranked number one in the nation by U.S. News & World Report for 22 years of the survey's 25 year history, most recently in 2013. For more information about Johns Hopkins Medicine, its research, education and clinical programs, and for the latest health, science and research news, visit http://www.hopkinsmedicine.org.

Vanessa Wasta | Eurek Alert!

More articles from Health and Medicine:

nachricht Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

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: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>