A team of researchers has genetically engineered normal immune cells to become specialized tumor fighters, demonstrating for the first time that these engineered cells can persist in the body and shrink large tumors in humans.
Two of the 17 people with advanced melanoma who received the experimental treatment saw their tumors shrink and were declared clinically free of disease more than a year and half after the therapy began, Steven A. Rosenberg of the National Cancer Institute and his colleagues report in a study published online by the journal Science at the Science Express website on 31 August. Science and Science Express are published by AAAS, the nonprofit science society.
So far, the therapy has only been used in this small group of melanoma patients, but Rosenberg says his team has demonstrated ways to engineer similar immune cells in the laboratory that would attack more common tumors such as breast, lung and liver cancers.
The technique developed by the Science researchers "represents the first time that gene manipulations have been shown to cause tumor regression in humans," Rosenberg says.
"This work marks an important next step in harnessing the power of our immune systems to fight cancer. The publication of this paper should help highlight the significant work to a broad spectrum of people, including patients, clinicians and those involved in basic research," said Stephen Simpson, Science's senior editor, immunology.
Rosenberg and colleagues have a long history of looking for ways to boost the body's natural immune defenses against cancer, focusing specifically on T cells, a special type of immune cell that can recognize and attack "foreign" cells such as those found in tumors. In their earlier experiments, the researchers removed tumor-fighting T cells from melanoma patients and multiplied these cells in the laboratory. After using chemotherapy to clear out a patient's old T cells, the researchers repopulated the patients' immune systems with these new fighters.
But some people with melanoma don't have these tumor-fighting T cells, and in other types of cancer it's difficult to identify T cells that attack tumors, Rosenberg says, so the researchers had to come up with a way to create these types of T cells from scratch.
T cells carry a receptor protein on their surface that recognizes specific molecules called antigens on tumor cells. The receptor's genetic makeup determines the antigen types that the T cell can recognize, so that some cells contain genes that make a T cell receptor that homes in on melanoma cells, while other cells contain genes that make a T cell receptor that recognizes breast or lung cancer cells.
With this in mind, Rosenberg and colleagues created tumor fighters by removing normal T cells from people with advanced metastatic melanoma, genetically engineering these normal cells to carry the receptor that recognizes melanoma cells and returning these "re-armed" cells to rebuild the patients' immune systems.
"We can take normal lymphocytes from patients and convert them to tumor-reactive cells," Rosenberg says, adding that the engineered cells could be tailored to fight tumors other than melanoma. "We've identified T cell receptors that will now recognize common cancers," he notes.
The newly engineered T cells showed signs of persistence in 15 of the patients in the study, making up at least 10 percent of their circulating T cells for at least two months after treatment. New T cell levels were higher in the two people whose tumors shrunk noticeably with the treatment.
Rosenberg and colleagues are now searching for ways to fine-tune the treatment so that greater numbers of the engineered T cells will survive and continue expressing their new receptor genes, since their expression does seem to wane over time, the Science researchers found.
Devising new ways to insert the receptor genes in the T cells, usually encoded in a retrovirus, has been one of the most challenging aspects of the treatment, Rosenberg says. "It's a lot of sophisticated molecular biology and most of our work is going into designing retroviruses, putting genes into cells efficiently and getting them expressed."
Natasha Pinol | EurekAlert!
Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology
Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven
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...
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....
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...
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...
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...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
18.10.2017 | Materials Sciences
18.10.2017 | Physics and Astronomy
18.10.2017 | Physics and Astronomy