{"649789":{"#nid":"649789","#data":{"type":"news","title":"Heat-Controllable CAR T-Cells Destroy Tumors and Prevent Relapse in New Study","body":[{"value":"\u003Cp\u003EA team of researchers led by bioengineers at the Georgia Institute of Technology is expanding the precision and ability of a revolutionary immunotherapy that is already transforming oncology. CAR T-Cell therapy has been hailed by patients, clinical-researchers, investors, and the media as a viable cure for some cancers.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ECAR T-Cell therapy involves engineering a patient\u0026rsquo;s T-cells, a type of white blood cell, in a lab. Then a chimeric antigen receptor (CAR) is added, and these customized immune cells are returned to the patient\u0026rsquo;s body, where they seek and destroy cancer cells. That\u0026rsquo;s how it works, when it works.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIt\u0026rsquo;s a new, evolving, and booming area of immunotherapy, with more than 500 clinical trials analyzing CAR T-cells for cancer treatment going on right now around the world.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;These therapies have proven to be remarkably effective for patients with liquid tumors \u0026ndash; so, tumors that are circulating in the blood, such as leukemia,\u0026rdquo; said \u003Ca href=\u0022https:\/\/bme.gatech.edu\/bme\/faculty\/Gabe-A.-Kwong\u0022\u003EGabe Kwong\u003C\/a\u003E, associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. \u0026ldquo;Unfortunately, for solid tumors \u0026ndash; sarcomas, carcinomas \u0026ndash; they don\u0026rsquo;t work well. There are many different reasons why. One huge problem is that the CAR T-cells are immunosuppressed by the tumor microenvironment.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EKwong and his collaborators are changing the environment and making some cell modifications of their own to enhance the way CAR T-cells fight cancer. They\u0026rsquo;ve added a genetic on-off switch to the cells and a developed a remote-control system that sends the modified T-cells on a precision invasion of the tumor microenvironment, where they kill the tumor and prevent a relapse. And they explain it all in a \u003Ca href=\u0022https:\/\/www.nature.com\/articles\/s41551-021-00781-2\u0022\u003Estudy published recently in the journal \u003Cem\u003ENature Biomedical Engineering\u003C\/em\u003E.\u003C\/a\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe latest study builds on the lab\u0026rsquo;s \u003Ca href=\u0022https:\/\/rh.gatech.edu\/news\/605259\/remote-control-shoots-laser-nano-gold-turn-cancer-killing-immune-cells\u0022\u003Ebody of work exploring remotely controlled cell therapies\u003C\/a\u003E, in which the researchers can precisely target tumors, wherever they are in the body, with a local deposition of heat. \u0026ldquo;And this heat basically activates the CAR T-cells inside the tumors, overcoming the problems of immunosuppression,\u0026rdquo; said Kwong.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EIn the earlier study, the researchers did not clinically treat tumors, but they are doing that now with the new work. To generate heat in a mouse\u0026rsquo;s tumor, they shone laser pulses from outside the animal\u0026rsquo;s body, onto the spot where a tumor is located. Gold nanorods delivered to the tumor turn the light waves into localized, mild heat, raising the temperature to 40-42 Celsius (104-107.6 F), just enough to activate the T-Cells\u0026rsquo; on-switch, but not so hot that it would damage healthy tissue, or the T-cells. Once turned on, the cells go to work, increasing the expression of cancer-fighting proteins.\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe real novelty, Kwong said, was in genetically engineering clinical-grade CAR T-Cells, something the team worked on for the past three years. Now, in addition to a switch that responds to heat, the researchers have added a few upgrades to the T-cells, rewiring them to produce molecules to stimulate the immune system.\u003C\/p\u003E\r\n\r\n\u003Cp\u003ELocalized production of these potent, engineered proteins (cytokines and Bispecific T-cell Engagers) has to be controlled precisely.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;These cancer-fighting proteins are really good at stimulating CAR T-cells, but they are too toxic to be used outside of tumors,\u0026rdquo; said Kwong. \u0026ldquo;They are too toxic to be delivered systemically. But with our approach we can localize these proteins safely. We get all the benefits without the drawbacks.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe latest study shows the system cured cancer in mice, and the team\u0026rsquo;s approach not only shrunk tumors but prevented relapse \u0026ndash; critical for long-term survival. Further studies will delve into additional tailoring of T-cells, as well as how heat will be deposited at the tumor site. A gentle laser was used\u0026nbsp;to heat the tumor site.\u0026nbsp;That won\u0026rsquo;t be the case when the technology moves on to human studies.\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026ldquo;We\u0026rsquo;ll use focused ultrasound, which is completely non-invasive and can target any site in the body,\u0026rdquo; Kwong said. \u0026ldquo;One of the limitations with laser is that it doesn\u0026rsquo;t penetrate very far in the body. So, if you have a deep-seated malignant tumor, that would be a problem. We want to eliminate problems.\u0026rdquo;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cem\u003EThe research was funded by the NIH Director\u0026rsquo;s New Innovator Award\u003C\/em\u003E\u003Cstrong\u003E\u003Cem\u003E (\u003C\/em\u003E\u003C\/strong\u003E\u003Cem\u003EDP2HD091793), the National Center for Advancing Translational Sciences (UL1TR000454), and the Shurl and Kay Curci Foundation. \u003C\/em\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003ECITATION:\u003C\/strong\u003E Ian C. Miller, Ali Zamat, Lee-Kai Sun, Hathaichanok Phuengkham, Adrian M. Harris, Lena Gamboa1, Jason Yang7, John P. Murad7, Saul J. Priceman, Gabriel A. Kwong.\u003Cstrong\u003E \u003C\/strong\u003E\u0026ldquo;\u003Ca href=\u0022https:\/\/www.nature.com\/articles\/s41551-021-00781-2\u0022\u003EEnhanced intratumoural activity of CAR T cells engineered to produce immunomodulators under photothermal control.\u003C\/a\u003E\u0026rdquo; (\u003Cem\u003ENature Biomedical Engineering\u003C\/em\u003E, August 2021)\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E\r\n\r\n\u003Cp\u003E\u003Cstrong\u003EAbout Georgia Tech \u003C\/strong\u003E\u003C\/p\u003E\r\n\r\n\u003Cp\u003EThe Georgia Institute of Technology, or Georgia Tech, is a top 10 public research university developing leaders who advance technology and improve the human condition. The Institute offers business, computing, design, engineering, liberal arts, and sciences degrees. Its nearly 40,000 students representing 50 states and 149 countries, study at the main campus in Atlanta, at campuses in France and China, and through distance and online learning. As a leading technological university, Georgia Tech is an engine of economic development for Georgia, the Southeast, and the nation, conducting more than $1 billion in research annually for government, industry, and society.\u003C\/p\u003E\r\n","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":"","field_summary_sentence":[{"value":"BME researchers enhance groundbreaking cancer therapy"}],"uid":"28153","created_gmt":"2021-08-17 23:18:23","changed_gmt":"2021-08-18 15:22:58","author":"Jerry Grillo","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2021-08-17T00:00:00-04:00","iso_date":"2021-08-17T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"649788":{"id":"649788","type":"image","title":"Zamat and Kwong","body":null,"created":"1629241906","gmt_created":"2021-08-17 23:11:46","changed":"1629241906","gmt_changed":"2021-08-17 23:11:46","alt":"","file":{"fid":"246643","name":"Zamat and Kwong 3.jpg","image_path":"\/sites\/default\/files\/images\/Zamat%20and%20Kwong%203.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/Zamat%20and%20Kwong%203.jpg","mime":"image\/jpeg","size":884265,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/Zamat%20and%20Kwong%203.jpg?itok=N8sr3z9t"}}},"media_ids":["649788"],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"},{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"140","name":"Cancer Research"}],"keywords":[{"id":"187423","name":"go-bio"},{"id":"187915","name":"go-researchnews"},{"id":"2470","name":"cancer therapy"},{"id":"188668","name":"CAR T-Cells"},{"id":"280","name":"Cancer research"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[{"id":"71891","name":"Health and Medicine"},{"id":"71881","name":"Science and Technology"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003EWriter: \u003Ca href=\u0022mailto:jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003C\/p\u003E\r\n","format":"limited_html"}],"email":["Jerry.grillo@ibb.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}