Immunotherapies — which make use of patients' own immune cells that have been augmented in the laboratory — have shown some early success in the treatment of blood cancers including certain types of leukemia.
For most cancers, however, cell-based therapies have been harder to develop, in large part because it has been difficult for investigators to train immune cells to specifically attack cancer cells without damaging normal, healthy cells in the body.
The treatment approach, known as adoptive cell transfer (ACT), involves engineering an immune cell called a T cell. In the ACT process, T cells are removed from a patient and a gene is added to allow the T cells to recognize a certain antigen on the surface of a cancer cell. The enhanced cells are grown in the laboratory and then infused back into the patient to seek out and attack cancer cells.
"We are getting better at working with these T cells and enhancing them so that we can get a powerful immunological response against cancer," Dr. Sadelain says. "The dilemma now is that we are concerned with limiting these responses and making them as targeted as possible to avoid potentially harmful side effects."
Cancer cells overproduce certain antigens, which can help T cells to recognize them, but those same antigens are often found in lower levels on healthy cells. "There are very few antigens, if any, that are found only on cancer cells," Dr. Sadelain explains.
"Now we are bringing in a completely new concept," he adds. "If there is no single unique antigen that is found on the surface of the cancer cell we want to target, we instead create T cells that recognize two different antigens found on the tumor cell — a signature that will be unique to that type of cancer — and only attack cells with both antigens, sparing the normal cells that express either antigen alone."
The new technique makes use of receptors known as chimeric antigen receptors (CARs), which allow T cells to target antigens on the surface of a tumor cell, coupled with another type of receptor called a chimeric costimulatory receptor (CCR), by which the T cells can recognize a second antigen.
The CAR and the CCR work together through a process known as balanced signaling, in which the presence of either antigen on its own is not enough to trigger the immune response. Only tumor cells that carry both antigens will be targeted.
In the Nature Biotechnology study, the team created T cells that carried a CAR for an antigen called PSMA and a CCR for an antigen called PSCA. Both PSMA and PSCA are found on prostate cancer cells. The investigators then generated mouse models of prostate cancer and infused the mice with the engineered cells. They found that the T cells attacked only tumors that carried antigens for both PSMA and PSCA.
"We are the first to test this concept and show that it works," Dr. Sadelain concludes. "We plan to develop clinical trials based on this approach, although we have not yet decided whether the first study will be a trial for prostate cancer or for a different type of cancer using two other antigens. Ultimately, our goal is to create targeted immunotherapies that are both potent and safe for patients."
In addition to members of Dr. Sadelain's laboratory, coauthors on the study included two researchers from TU Dresden in Germany.
This work was supported by philanthropic funds provided by the Mr. William H. and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research, the Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center, the Major Family Fund for Cancer Research at Memorial Sloan-Kettering, Mr. and Mrs. Joel S. Mallah, and Mr. Lewis Sanders.
Andrea Molinatti | EurekAlert!
New catalyst controls activation of a carbon-hydrogen bond
21.11.2017 | Emory Health Sciences
The main switch
21.11.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
21.11.2017 | Physics and Astronomy
21.11.2017 | Physics and Astronomy
21.11.2017 | Life Sciences