{"id":21490,"date":"2021-09-14T12:13:22","date_gmt":"2021-09-14T06:28:22","guid":{"rendered":"https:\/\/www.revoscience.com\/en\/?p=21490"},"modified":"2021-09-14T12:13:24","modified_gmt":"2021-09-14T06:28:24","slug":"scientists-design-molecular-code-that-powers-up-cancer-fighting-immune-cells","status":"publish","type":"post","link":"https:\/\/www.revoscience.com\/en\/scientists-design-molecular-code-that-powers-up-cancer-fighting-immune-cells\/","title":{"rendered":"Scientists design molecular code that powers up cancer-fighting immune cells"},"content":{"rendered":"\n
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A synthetic molecular code shows promise towards improving the response of some cancer patients to immunotherapy treatments. The approach involves using a molecule that can provide energy to anti-cancer immune cells, increasing their numbers and improving their longevity. <\/p>\n\n\n\n

Cancer cells express molecules that can target a receptor to inactivate tumor-fighting T cells. \u201cTherapeutics that block the immunosuppressive molecule, called PD-L1, from binding to the T cell surface receptor, called PD-1, have revolutionized cancer treatment. However, more than half of cancer patients don\u2019t respond well to this immunotherapy,\u201d explains Madhu Malinee, the study\u2019s first author.<\/p>\n\n\n\n

\u201cOne of the major reasons for this unresponsiveness is that these patients have an insufficient number of T cells that also become exhausted because they don\u2019t have enough active energy-providing mitochondria,\u201d says Ganesh Namasivayam Pandian of Kyoto University\u2019s Institute of Integrated Cell Material Sciences (iCeMS).<\/p>\n\n\n\n

The team wanted to find a way to increase the mitochondria in T cells to improve cancer patient response to PD-1 blockade monotherapy. Their aim was to activate a molecule, called PGC-1, which regulates the expression of genes involved in energy metabolism. A major roadblock to achieving this, however, has been finding a way to selectively target PGC-1.<\/p>\n\n\n\n

To do this, Sugiyama and colleagues used a compound, called pyrrole-imidazole polyamide (PIP), that can be programmed to target a specific DNA sequence. They assembled it as a molecular code, called EnPGC-1, that can activate PGC-1.<\/p>\n\n\n\n

The team found that EnPGC-1 activated the mitochondria of mouse T cells in the laboratory, which led to an increase in T cell numbers and their longevity.<\/p>\n\n\n\n

They then gave tumor-bearing mice a combination of EnPGC-1 with PD-1 blockade immunotherapy and found the strategy enhanced anti-tumor immunity in the mice and improved their survival.<\/p>\n\n\n\n

\u201cSince PGC-1 signaling is known to be essential for energy metabolism, EnPGC-1 also has potential for being developed as a drug to treat other diseases, like type 2 diabetes and hyperlipidemia,\u201d says Madhu.<\/p>\n\n\n\n

\u201cFurther improvements are needed before the approach can be tested for clinical use\u201d, adds Ganesh. For example, the team aims to find ways to deliver EnPGC-1 specifically to T cells to reduce its off-target effects.<\/p>\n\n\n\n

The findings were published by Kyoto University scientists, led by Hiroshi Sugiyama, in the journal\u00a0Cell Chemical Biology.<\/p>\n\n\n\n

Reference:<\/p>\n\n\n\n

DOI:<\/strong>https:\/\/doi.org\/10.1016\/j.chembiol.2021.08.001<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

A synthetic molecular code shows promise towards improving the response of some cancer patients to immunotherapy treatments.<\/p>\n","protected":false},"author":2,"featured_media":21491,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,17],"tags":[],"class_list":["post-21490","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health","category-research"],"featured_image_urls":{"full":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya.jpg",1100,663,false],"thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya-200x200.jpg",200,200,true],"medium":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya-664x400.jpg",664,400,true],"medium_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya-768x463.jpg",750,452,true],"large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya-675x407.jpg",675,407,true],"1536x1536":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya.jpg",1100,663,false],"2048x2048":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya.jpg",1100,663,false],"ultp_layout_landscape_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya.jpg",1100,663,false],"ultp_layout_landscape":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya.jpg",870,524,false],"ultp_layout_portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya.jpg",600,362,false],"ultp_layout_square":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya.jpg",600,362,false],"newspaper-x-single-post":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya-760x490.jpg",760,490,true],"newspaper-x-recent-post-big":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya-550x360.jpg",550,360,true],"newspaper-x-recent-post-list-image":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya-95x65.jpg",95,65,true],"web-stories-poster-portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya.jpg",640,386,false],"web-stories-publisher-logo":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya.jpg",96,58,false],"web-stories-thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2021\/09\/namasivayam-celchembiol-takamiya.jpg",150,90,false]},"author_info":{"info":["RevoScience"]},"category_info":"Health<\/a> Research<\/a>","tag_info":"Research","comment_count":"0","_links":{"self":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/21490","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/comments?post=21490"}],"version-history":[{"count":0,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/21490\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media\/21491"}],"wp:attachment":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media?parent=21490"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/categories?post=21490"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/tags?post=21490"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}