Done in mouse models, the study serves as first proof-of-principle that blood stem cells, which make every cell type found in blood, can be genetically altered in a living organism to create an army of melanoma-fighting T-cells, said Jerome Zack, study senior author and a scientist with UCLA’s Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
“We knew from previous studies that we could generate engineered T-cells, but would they work to fight cancer in a relevant model of human disease, such as melanoma,” said Zack, a professor of medicine and microbiology, immunology, and molecular genetics in Life Sciences. “We found with this study that they do work in a human model to fight cancer, and it’s a pretty exciting finding.”
The study appears Nov. 28, 2011 in the early online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences.
Researchers used a T-cell receptor from a cancer patient cloned by other scientists that seeks out an antigen expressed by this type of melanoma. They then genetically engineered the human blood stem cells by importing genes for the T-cell receptor into the stem cell nucleus using a viral vehicle. The genes integrate with the cell DNA and are permanently incorporated into the blood stem cells, theoretically enabling them to produce melanoma-fighting cells indefinitely and when needed, said Dimitrios N. Vatakis, study first author and an assistant researcher in Zack’s lab.
“The nice thing about this approach is a few engineered stem cells can turn into an army of T-cells that will respond to the presence of this melanoma antigen,” Vatakis said. “These cells can exist in the periphery of the blood and if they detect the melanoma antigen, they can replicate to fight the cancer.”
In the study, the engineered blood stem cells were placed into human thymus tissue that had been implanted in the mice, allowing Zack and his team to study the human immune system reaction to melanoma in a living organism. Over time, about six weeks, the engineered blood stem cells developed into a large population of mature, melanoma-specific T-cells that were able to target the right cancer cells.
The mice were then implanted with two types of melanoma, one that expressed the antigen complex that attracts the engineered T-cells and one tumor that did not. The engineered cells specifically went after the antigen-expressing melanoma, leaving the control tumor alone, Zack said.
The study included nine mice. In four animals, the antigen-expressing melanomas were completely eliminated. In the other five mice, the antigen-expressing melanomas decreased in size, Zack said, an impressive finding.
Response was assessed not only by measuring physical tumor size, but by monitoring the cancer’s metabolic activity using Positron Emission Tomography (PET), which measures how much energy the cancer is “eating” to drive its growth.
“We were very happy to see that four tumors were completely gone and the rest had regressed, both by measuring their size and actually seeing their metabolic activity through PET,” Zack said.
This approach to immune system engineering has intriguing implications, Zack said. T-cells can be engineered to fight disease, but their function is not long-lasting in most cases. More engineered T-cells ultimately are needed to sustain a response. This approach engineers the cells that give rise to the T-cells, so “fresh” cancer-killing cells could be generated when needed, perhaps protecting against cancer recurrence later.
Going forward, the team would like to test this approach in clinical trials. One possible approach would be to engineer both the peripheral T-cells and the blood stem cells that give rise to T-cells. The peripheral T-cells would serve as the front line cancer fighters, while the blood stem cells are creating a second wave of warriors to take up the battle as the front line T-cells are losing function.
Zack said he hopes this engineered immunity approach will translate to other cancers as well, including breast and prostate cancers.
The four-year study was funded in part by the National Institutes of Health, the California Institute for Regenerative Medicine, the Caltech-UCLA Joint Center for Translational Medicine, UCLA Center for AIDS Research and the UCLA AIDS Institute.
UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2011, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 11 of the last 12 years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.
The stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLA’s Jonsson Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science. To learn more about the center, visit our web site at http://www.stemcell.ucla.edu. To learn more about the center, visit our web site at http://www.stemcell.ucla.edu.
Further reports about: > Aids > Cancer > Comprehensive Cancer Center > Medicine > Regenerative Therapien > Stem cell innovation > T-cell > UCLA > blood stem cells > cell death > clinical application > human embryonic stem cell > immune system > living organism > melanoma > metabolic activity > methanol fuel cells > molecular genetic > mouse model > prostate cancer > stem cells
Kidney tumor: Genetic trigger discovered
18.06.2018 | Julius-Maximilians-Universität Würzburg
New type of photosynthesis discovered
18.06.2018 | Imperial College London
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
Light detection and control lies at the heart of many modern device applications, such as smartphone cameras. Using graphene as a light-sensitive material for...
Water molecules exist in two different forms with almost identical physical properties. For the first time, researchers have succeeded in separating the two forms to show that they can exhibit different chemical reactivities. These results were reported by researchers from the University of Basel and their colleagues in Hamburg in the scientific journal Nature Communications.
From a chemical perspective, water is a molecule in which a single oxygen atom is linked to two hydrogen atoms. It is less well known that water exists in two...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
18.06.2018 | Life Sciences
18.06.2018 | Life Sciences
18.06.2018 | Automotive Engineering