{"675091":{"#nid":"675091","#data":{"type":"news","title":"Nanowires Create Elite Warriors to Enhance T Cell Therapy","body":[{"value":"\u003Cp\u003EAdoptive T-cell therapy has revolutionized medicine. A patient\u2019s T-cells \u2014 a type of white blood cell that is part of the body\u2019s immune system \u2014 are extracted and modified in a lab and then infused back into the body, to seek and destroy infection, or cancer cells.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ENow Georgia Tech bioengineer\u0026nbsp;\u003Ca href=\u0022https:\/\/singhlab.bme.gatech.edu\/\u0022\u003EAnkur Singh\u003C\/a\u003E and his research team have developed a method to improve this pioneering immunotherapy.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ETheir solution involves using nanowires to deliver therapeutic miRNA to T-cells. This new modification process retains the cells\u2019 na\u00efve state, which means they\u2019ll be even better disease fighters when they\u2019re infused back into a patient.\u003C\/p\u003E\u003Cp\u003E\u201cBy delivering miRNA in na\u00efve T cells, we have basically prepared an infantry, ready to deploy,\u201d Singh said. \u201cAnd when these na\u00efve cells are stimulated and activated in the presence of disease, it\u2019s like they\u2019ve been converted into samurais.\u201d\u003C\/p\u003E\u003Ch4\u003ELean and Mean\u003C\/h4\u003E\u003Cp\u003ECurrently in adoptive T-cell therapy, the cells become stimulated and preactivated in the lab when they are modified, losing their na\u00efve state. Singh\u2019s new technique overcomes this limitation. The approach is described in a\u0026nbsp;\u003Ca href=\u0022https:\/\/www.nature.com\/articles\/s41565-024-01649-7\u0022\u003Enew study\u003C\/a\u003E published in the journal \u003Cem\u003ENature Nanotechnology\u003C\/em\u003E.\u003C\/p\u003E\u003Cp\u003E\u201cNa\u00efve T-cells are more useful for immunotherapy because they have not yet been preactivated, which means they can be more easily manipulated to adopt desired therapeutic functions,\u201d said Singh, the Carl Ring Family Professor in the\u0026nbsp;\u003Ca href=\u0022https:\/\/www.me.gatech.edu\/\u0022\u003EWoodruff School of Mechanical Engineering\u003C\/a\u003E and the\u0026nbsp;\u003Ca href=\u0022https:\/\/bme.gatech.edu\/bme\/\u0022\u003EWallace H. Coulter Department of Biomedical Engineering\u003C\/a\u003E.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EThe raw recruits of the immune system, na\u00efve T-cells are white blood cells that haven\u2019t been tested in battle yet. But these cellular recruits are robust, impressionable, and adaptable \u2014 ready and eager for programming.\u003C\/p\u003E\u003Cp\u003E\u201cThis process creates a well-programmed na\u00efve T-cell ideal for enhancing immune responses against specific targets, such as tumors or pathogens,\u201d said Singh.\u003C\/p\u003E\u003Cp\u003EThe precise programming na\u00efve T-cells receive sets the foundational stage for a more successful disease fighting future, as compared to preactivated cells.\u003C\/p\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Ch4\u003E\u003Cstrong\u003EGiving Fighter Cells a Boost\u003C\/strong\u003E\u003C\/h4\u003E\u003Cp\u003EWithin the body, na\u00efve T-cells become activated when they receive a danger signal from antigens, which are part of disease-causing pathogens, but they send a signal to T-cells that activate the immune system.\u003C\/p\u003E\u003Cp\u003EAdoptive T-cell therapy is used against aggressive diseases that overwhelm the body\u2019s defense system. Scientists give the patient\u2019s T-cells a therapeutic boost in the lab, loading them up with additional medicine and chemically preactivating them.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EThat\u2019s when the cells lose their na\u00efve state. When infused back into the patient, these modified T-cells are an effective infantry against disease \u2014 but they are prone to becoming exhausted. They aren\u2019t samurai. Na\u00efve T-cells, though, being the young, programmable recruits that they are, could be.\u003C\/p\u003E\u003Cp\u003EThe question for Singh and his team was: How do we give cells that therapeutic boost without preactivating them, thereby losing that pristine, highly suggestable na\u00efve state? Their answer: Nanowires.\u003C\/p\u003E\u003Ch4\u003E\u003Cstrong\u003ENanoPrecision: The Pointed Solution\u003C\/strong\u003E\u003C\/h4\u003E\u003Cp\u003ESingh wanted to enhance na\u00efve T-cells with a dose of miRNA. miRNA is a molecule that, when used as a therapeutic, works as a kind of volume knob for genes, turning their activity up or down to keep infection and cancer in check. The miRNA for this study was developed in part by the study\u2019s co-author, Andrew Grimson of Cornell University.\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cp\u003E\u201cIf we could find a way to forcibly enter the cells without damaging them, we could achieve our goal to deliver the miRNA into na\u00efve T cells without preactivating them,\u201d Singh explained.\u003C\/p\u003E\u003Cp\u003ETraditional modification in the lab involves binding immune receptors to T-cells, enabling the uptake of miRNA or any genetic material (which results in loss of the na\u00efve state). \u201cBut nanowires do not engage receptors and thus do not activate cells, so they retain their na\u00efve state,\u201d Singh said.\u003C\/p\u003E\u003Cp\u003EThe nanowires, silicon wafers made with specialized tools at Georgia Tech\u2019s\u0026nbsp;\u003Ca href=\u0022https:\/\/research.gatech.edu\/nano\u0022\u003EInstitute for Electronics and Nanotechnology\u003C\/a\u003E, form a fine needle bed. Cells are placed on the nanowires, which easily penetrate the cells and deliver their miRNA over several hours. Then the cells with miRNA are flushed out from the tops of the nanowires, activated, eventually infused back into the patient. These programmed cells can kill enemies efficiently over an extended time period.\u003C\/p\u003E\u003Cp\u003E\u201cWe believe this approach will be a real gamechanger for adoptive immunotherapies, because we now have the ability to produce T-cells with predictable fates,\u201d says Brian Rudd, a professor of immunology at Cornell University, and co-senior author of the study with Singh.\u003C\/p\u003E\u003Cp\u003EThe researchers tested their work in two separate infectious disease animal models at Cornell for this study, and Singh described the results as \u201ca robust performance in infection control.\u201d\u003C\/p\u003E\u003Cp\u003EIn the next phase of study, the researchers will up the ante, moving from infectious disease to test their cellular super soldiers against cancer and move toward translation to the clinical setting.\u0026nbsp; New funding from the Georgia Clinical \u0026amp; Translational Science Alliance is supporting Singh\u2019s research.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECITATION:\u003C\/strong\u003E\u0026nbsp;\u0026nbsp;Kristel J. Yee Mon, Sungwoong Kim, Zhonghao Dai, Jessica D. West, Hongya Zhu5, Ritika Jain, Andrew Grimson, Brian D. Rudd, Ankur Singh. \u003Ca href=\u0022https:\/\/www.nature.com\/articles\/s41565-024-01649-7\u0022\u003E\u201cFunctionalized nanowires for miRNA-mediated therapeutic programming of na\u00efve T cells,\u201d\u003C\/a\u003E \u003Cem\u003ENature Nanotechnology\u003C\/em\u003E.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EFUNDING:\u003C\/strong\u003E Curci Foundation, NSF (EEC-1648035, ECCS-2025462, ECCS-1542081), NIH (5R01AI132738-06, 1R01CA266052-01, 1R01CA238745-01A1, U01CA280984-01, R01AI110613 and U01AI131348).\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003E\u003Cem\u003EResearchers at Georgia Tech have developed a method using nanowires to deliver miRNA to T-cells, preserving their na\u00efve state and significantly enhancing their effectiveness in adoptive T-cell therapy for fighting infections and potentially cancer.\u003C\/em\u003E\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Researchers at Georgia Tech have developed a method using nanowires to deliver miRNA to T-cells, preserving their na\u00efve state and significantly enhancing their effectiveness in adoptive T-cell therapy for fighting infections and potentially cancer."}],"uid":"28153","created_gmt":"2024-06-12 14:09:49","changed_gmt":"2024-06-12 17:43:33","author":"Jerry Grillo","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2024-06-12T00:00:00-04:00","iso_date":"2024-06-12T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"674172":{"id":"674172","type":"image","title":"Ankur Singh","body":"\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cp\u003EAnkur Singh has developed a new way of programming T cells that retains their na\u00efve state, making them better fighters. \u2014 Photo by Jerry Grillo\u003C\/p\u003E\u003C\/div\u003E\u003Cdiv\u003E\u0026nbsp;\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp\u003E\u003Cbr\u003E\u003Cbr\u003E\u0026nbsp;\u003C\/p\u003E","created":"1718200954","gmt_created":"2024-06-12 14:02:34","changed":"1718201119","gmt_changed":"2024-06-12 14:05:19","alt":"Ankur Singh","file":{"fid":"257652","name":"ankur1.jpg","image_path":"\/sites\/default\/files\/2024\/06\/12\/ankur1.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/2024\/06\/12\/ankur1.jpg","mime":"image\/jpeg","size":7331552,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/2024\/06\/12\/ankur1.jpg?itok=aUhlcb_c"}},"674173":{"id":"674173","type":"image","title":"nanowires cells","body":"\u003Cp\u003EThis is an image of a T cell on a nanowire array. The arrow indicates where a nanowire has penetrated the cell, delivering therapeutic miRNA.\u003C\/p\u003E","created":"1718201149","gmt_created":"2024-06-12 14:05:49","changed":"1718201202","gmt_changed":"2024-06-12 14:06:42","alt":"Nanowires and cell","file":{"fid":"257653","name":"nanowire cell.jpg","image_path":"\/sites\/default\/files\/2024\/06\/12\/nanowire%20cell.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/2024\/06\/12\/nanowire%20cell.jpg","mime":"image\/jpeg","size":158813,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/2024\/06\/12\/nanowire%20cell.jpg?itok=cpBiHfWS"}}},"media_ids":["674172","674173"],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"},{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"138","name":"Biotechnology, Health, Bioengineering, Genetics"},{"id":"145","name":"Engineering"},{"id":"146","name":"Life Sciences and Biology"},{"id":"149","name":"Nanotechnology and Nanoscience"},{"id":"135","name":"Research"}],"keywords":[{"id":"187915","name":"go-researchnews"},{"id":"187423","name":"go-bio"},{"id":"7074","name":"nanowires"},{"id":"179643","name":"T cell activation"},{"id":"9513","name":"Cancer Reserach"},{"id":"187433","name":"go-ien"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[{"id":"71891","name":"Health and Medicine"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003EJerry Grillo\u003C\/p\u003E","format":"limited_html"}],"email":["Jerry.grillo@ibb.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}