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Cell therapies, including infusion of native or genetically modified immune cells, are designed to recognize and destroy cancer cells. This study develops a synthetic circuit that reprograms B cells using a tumor-detection sensor, a promoter-derived transducer, and an effector reporter or therapeutic output. The circuit distinguishes target-antigen expressing tumors in a dose-dependent manner in vitro, and secreted engineered antibodies enable synergistic effector amplification through Fc receptor recognition. Future work will assess therapeutic potential in vivo and enable personalized cancer treatment by adapting sensors and effector molecules.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-synthetic-circuit-empowering-reprogrammed-b-cells-for-therapeutic-proteins-expression-regulated-by-tumor-detection/338005/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/a-synthetic-circuit-empowering-reprogrammed-b-cells-for-therapeutic-proteins-expression-regulated-by-tumor-detection/338005.png","ImageObject",300,407,{"name":92,"@type":93},"Oliver","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the purpose of the synthetic circuit in this study?","Question",{"text":113,"@type":114},"The circuit reprograms B cells to drive expression of therapeutic proteins in a way regulated by recognition of tumor-associated target antigens.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How is tumor detection implemented in the circuit?",{"text":118,"@type":114},"A sensor element recognizes the target antigen and triggers signaling that activates a promoter-based transducer, leading to effector expression.",{"name":120,"@type":111,"acceptedAnswer":121},"What was improved by replacing the sensor with an immunoglobulin expression cassette?",{"text":122,"@type":114},"The new sensor can be membrane-anchored or secreted depending on B-cell maturation status, enabling simultaneous circuit activation and secretion of transgenic antibodies against the targeted antigen.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},338005,1790673883,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":29,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},8796095461610,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","A Synthetic Circuit Empowering Reprogrammed B Cells for Therapeutic Proteins Expression Regulated by Tumor  \nDetection  \nAudrey Page, Marie Delles, Didier Nègre, Caroline Costa, Floriane Fusil,  \nand François-Loïc Cosset  \nAbstract: Cancer remains a leading cause of death worldwide, but immunotherapies hold promises to cure it by awaking the patient’s immune system to provide long-term protection. Cell therapies, involving the infusion of immune cells, either directly or genetically modified, are being developed to recognize and destroy cancer cells. Here, we explored the potential of a new synthetic circuit toreprogram B cells to cure cancers. This circuit consists in a sensor (a membrane-anchored IgG1), a transducer (a fragment of the NR4A1 promoter) and an effector molecule. Upon recognition of its target, this sensor triggers signaling pathways leading to the activation of the transducer and to effector expression (here, a reporter molecule) . We showed that this circuit could discriminate tumors expressing the target antigen from those that did not, in a dose dependent manner in vitro. Going further, we replaced the original membraneanchored sensor by an immunoglobulin expression cassette that cannot only be membrane-anchored but also be secreted depending on B-cell maturation status. This allowed concomitant activation of the circuit and secretion of transgenic antibodies directed against the targeted antigen. Of note, these antibodies could correctly bind their target and were recognized by FcR expressed at the surface of immune cells, which should synergically amplify the action of the effector. The potential of reprogrammed B cells remains to be assessed in vivo by implementing a therapeutic effector. In the future, B-cell reprogramming platforms should allow personalized cancer treatment by adapting both the sensor and the therapeutic effectors to patients.  \nKey Words: B cells, synthetic circuits, synthetic immunology, cell reprogramming, cell therapy, autologous transfer, personalised medicine  \n(J Immunother 2024;47:233–238)  \nReceived for publication February 1, 2024; accepted April 10, 2024 . From the CIRI - Centre International de Recherche en Infectiologie, Univ Lyon, Universit Claude Bernard Lyon 1, Lyon, France.  \nA.P., F.F., and F.-L.C. designed the project. A.P., F.F. and F.-L.C. coordinated the project, reviewed and edited the manuscript before submission. A.P. designed, performed experiments, wrote the initial draft and revised subsequent drafts. M.D. and D.N. performed experiments. C.C. produced LVs. All authors have read and agreed to the published manuscript.  \nF.F. and F.-L.C.: conjointly supervised this work.  \nReprints: François-Loïc Cosset, CIRI: Centre International de Recherche en Infectiologie, Lyon 69007, France (e-mail: fl[cosset@ens-lyon.fr](cosset@ens-lyon.fr)) .  \nSupplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal’s website, [www.immunotherapy-journal.com](www.immunotherapy-journal.com).  \nCopyright © 2024 The Author(s) . Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.  \nDOI: 10.1097/CJI.0000000000000524  \nJ Immunother 􀀁 Volume 47, Number 7, September 2024  \nC ancers nowadays are still one of the major causes of  \ndeath worldwide accounting for around 10 millions of deaths per year. The past decades have faced unprecedent progresses in immunotherapies, whose aim is to awake the patient’s immune system, among which cell therapies. While most of the approaches focused on T cells, B cells have been underestimated; yet, their intrinsic properties, especially their capacity t","cbCaipQiITMduGPh","https://ap.wps.com/l/cbCaipQiITMduGPh","pdf",605840,"English","# Abstract\n# Introduction\n# Results","[{\"question\":\"What is the purpose of the synthetic circuit in this study?\",\"answer\":\"The circuit reprograms B cells to drive expression of therapeutic proteins in a way regulated by recognition of tumor-associated target antigens.\"},{\"question\":\"How is tumor detection implemented in the circuit?\",\"answer\":\"A sensor element recognizes the target antigen and triggers signaling that activates a promoter-based transducer, leading to effector expression.\"},{\"question\":\"What was improved by replacing the sensor with an immunoglobulin expression cassette?\",\"answer\":\"The new sensor can be membrane-anchored or secreted depending on B-cell maturation status, enabling simultaneous circuit activation and secretion of transgenic antibodies against the targeted antigen.\"}]","A Synthetic Circuit Empowering Reprogrammed B Cells for Therapeutic Proteins Expression Regulated by Tumor Detection | PDF",1790021543,15]