Researchers at the Cedars-Sinai Maxine Dunitz Neurosurgical Institute and Department of Neurosurgery identified immune system targets on cancer stem cells – cells from which malignant brain tumors are believed to originate and regenerate – and created an experimental vaccine to attack them.
Results of laboratory and animal studies are published in the online edition of Stem Cells Translational Medicine, and will appear in the March 2014 print edition. A Phase I safety study in human volunteers with recurrent glioblastoma multiforme, the most common and aggressive brain tumor in adults, is underway.
Like normal stem cells, cancer stem cells have the ability to self-renew and generate new cells, but instead of producing healthy cells, they create cancer cells. In theory, if the cancer stem cells can be destroyed, a tumor may not be able to sustain itself, but if the cancer originators are not removed or destroyed, a tumor will continue to return despite the use of existing cancer-killing therapies.
The researchers identified certain fragments of a protein – CD133 – that is found on cancer stem cells of some brain tumors and other cancers. In the laboratory, they cultured the proteins with dendritic cells, the immune system's most powerful antigen-presenting cells, which are responsible for helping the immune system recognize and attack invaders.
Studies in lab mice showed that the resulting vaccine was able to stimulate an immune response against the CD133 proteins without causing side effects such as an autoimmune reaction against normal cells or organs.
"CD133 is one of several proteins made at high levels in the cancer stem cells of glioblastoma multiforme. Because this protein appears to be associated with resistance of the cancer stem cells to treatment with radiation or chemotherapy or both, we see it as an ideal target for immunotherapy. We have found at least two fragments of the protein that can be targeted to trigger an immune response to kill tumor cells. We don't know yet if the response would be strong enough to prevent a tumor from coming back, but we now have a human clinical trial underway to assess safety for further study," said John Yu, MD, vice chair of the Department of Neurosurgery, director of surgical neuro-oncology, medical director of the Brain Tumor Center and neurosurgical director of the Gamma Knife Program at Cedars-Sinai. He is senior author of the journal article.
With standard care, which includes surgery, radiation treatment and chemotherapy, median length of survival is 15 months for patients diagnosed with glioblastoma multiforme. Cedars-Sinai researchers have studied dendritic cell immunotherapy since 1997, with the first patient human clinical trial launched in 1998.
The dendritic cell vaccines are produced by the biotechnology company ImmunoCellular Therapeutics Ltd., which funded this study. Cedars-Sinai owns equity in the company, and certain rights in the vaccine technology and corresponding intellectual property have been exclusively licensed by Cedars-Sinai to ImmunoCellular Therapeutics.
Two members of the research team and authors of this article have ties to the company. Yu, senior author, owns stock in the company and is its founder, chief scientific officer and chair of the board of directors. James Bender, PhD, MPH, a co-author, is ImmunoCellular Therapeutics' vice president for product development and manufacturing.
Researchers from Torrey Pines Institute for Molecular Studies also participated in the study.
Citation: Stem Cells Translational Medicine, "Identification of novel HLA-A*0201-restricted, cytotoxic T lymphocyte epitopes on CD133 for cancer stem cell immunotherapy," Available online 12/27/13. To appear in the March, 2014, print edition.
Sandy Van | Cedars-Sinai News
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy