[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-435698-105":59,"doc-detail-435698-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","engineered-lactobacillus-expressing-tumor-killing-cytokines-a-novel-biotherapeutic","Engineered Lactobacillus expressing tumor-killing cytokines - a novel biotherapeutic","","Cancer causes over 10 million deaths annually, and most cases involve solid tumors. Systemic cytokine delivery is constrained by severe toxicity, exemplified by high-dose IL-2 therapy producing grade 3–4 adverse effects in over 60% of patients and ~4% treatment-related mortality. Engineered Lactobacillus strains that deliver tumor-killing cytokines such as IL-12, IL-15, and TRAIL provide localized immune activation with reduced systemic risk. Preclinical results show marked tumor suppression in colorectal, pancreatic, and melanoma models.",{"@graph":69,"@context":122},[70,84,105],{"@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/engineered-lactobacillus-expressing-tumor-killing-cytokines-a-novel-biotherapeutic/435698/",{"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/engineered-lactobacillus-expressing-tumor-killing-cytokines-a-novel-biotherapeutic/435698.png","ImageObject",300,407,{"name":92,"@type":93},"acoobca","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is systemic cytokine therapy limited for cancer treatment?","Question",{"text":112,"@type":113},"Systemic cytokine administration causes severe toxicity. High-dose IL-2 therapy is associated with grade 3–4 toxicities in over 60% of patients and treatment-related mortality around 4%.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What is the proposed biotherapeutic strategy in this letter?",{"text":117,"@type":113},"Engineered Lactobacillus strains are designed to express tumor-killing cytokines such as IL-12, IL-15, and TRAIL. The aim is localized, tumor-specific immune activation while avoiding dose-limiting systemic toxicity.",{"name":119,"@type":110,"acceptedAnswer":120},"What preclinical outcomes are reported for engineered Lactobacillus?",{"text":121,"@type":113},"The letter reports that IL-12–secreting L. plantarum can reduce colorectal tumor volume by up to 65%, TRAIL-expressing L. casei can reduce pancreatic tumor mass by about 40%, and IL-15–producing L. reuteri can enhance intratumoral CD8+ infiltration and improve survival in murine melanoma models.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},435698,1791350987,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":24,"preview_page_count":4},3985747870733,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Letter to the Editor  \nEngineered Lactobacillus expressing tumor-killing cytokines: a novel biotherapeutic  \nMuhammad Shahid Mehmood, MPhila , Maryam Abid, FESMOb , Fatima Hajj, MDc ,*  \nAbstract  \nCancer accounts for over 10 million deaths annually, with solid tumors responsible for nearly 90% of cases worldwide. Systemic cytokine administration remains limited by severe toxicity, high-dose interleukin-2 (IL-2) therapy induces grade 3–4 adverse effects in >60% of patients, and treatment-related mortality is around 4% . In this context, engineered Lactobacillus strains designed to express tumor-killing cytokines such as IL-12, IL-15, and TRAIL represent a novel biotherapeutic strategy that combines microbial safety with precision immune activation. Experimental evidence shows that Lactobacillus plantarum secreting IL-12 reduces colorectal tumor volume by 65%, L. casei expressing TRAIL decreases pancreatic tumor mass by 40%, and L. reuteri producing IL-15 enhances CD8+ T-cell infiltration by 45% and improves survival by 30% in murine models. These data illustrate that cytokineexpressing probiotics can replicate the efficacy of systemic cytokine therapy while avoiding dose-limiting toxicity. Integrating synthetic biology tools such as inducible promoters and biosafety kill switches further refines control and containment, making this a viable candidate for translational development. The convergence of immunotherapy and microbiome engineering thus establishes engineered Lactobacillus as a novel, locally acting, and low-toxicity antitumor biotherapeutic with the potential to reshape next-generation cancer treatment.  \nKeywords: cancer immunotherapy, cytokine delivery, engineered Lactobacillus , IL-12, IL-15, probiotics, TRAIL, translational oncology  \nTo the Editor,  \nGlobally, cancer remains a leading cause of mortality, responsible for 10 million deaths annually, with solid tumors accounting for nearly 90% of these cases [1] . Systemic cytokine administration continues to result in high toxicity; for example, high-dose interleukin-2 (IL-2) therapy is associated with grade 3–4 toxicities in over 60% of patients and treatment-related mortality approaching 4%[2] . These challenges underscore the need for safer, targeted delivery systems. Engineered Lactobacillus expressing tumor-killing cytokines offers a transformative and localized alternative to systemic cytokine therapy, enabling tumor-specific immune activation while minimizing systemic toxicity.  \nRecent data demonstrate remarkable preclinical efficacy. Ina murine colorectal cancer model, L. plantarum engineered to  \naFaculty of Veterinary Science, Institute of Microbiology, University of Agriculture, Faisalabad, Pakistan, bDepartment of Oncology and Radiotherapy, King Edward Medical University, Lahore, Pakistan and cFaculty of Medical Sciences, Lebanese University, Beirut, Lebanon  \nSponsorships or competing interests that may be relevant to content are disclosed at the end of this article.  \n*Corresponding author. Address: Faculty of Medical Sciences, Lebanese University, P.O. Box 6573/14, Beirut, Lebanon. Tel.: +961 81001507.  \nE-mail: [fatimalalala2001@gmail.com](fatimalalala2001@gmail.com) (F. Hajj).  \nCopyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons AttributionNon 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. Annals of Medicine & Surgery (2026) 88:1040–1041  \nReceived 9 October 2025; Accepted 11 November 2025  \nPublished online 3 December 2025  \n[http://dx.doi.org/10.1097/MS9.0000000000004400](http://dx.doi.org/10.1097/MS9.0000000000004400)  \nsecrete IL-12 reduced tumor volume by up to 65% within 21 days compared to controls (P \u003C 0.01)[3] . Similarly, L. casei expressing TRAIL ind","cbCaihgyn3mzVrcg","https://ap.wps.com/l/cbCaihgyn3mzVrcg","pdf",190912,"English","# Letter to the Editor\n## Abstract\n## To the Editor\n## Preclinical efficacy and mechanisms\n## Advantages of probiotic vectors and synthetic-biology control\n## Ethical approval, consent, and funding","[{\"question\":\"Why is systemic cytokine therapy limited for cancer treatment?\",\"answer\":\"Systemic cytokine administration causes severe toxicity. High-dose IL-2 therapy is associated with grade 3–4 toxicities in over 60% of patients and treatment-related mortality around 4%.\"},{\"question\":\"What is the proposed biotherapeutic strategy in this letter?\",\"answer\":\"Engineered Lactobacillus strains are designed to express tumor-killing cytokines such as IL-12, IL-15, and TRAIL. The aim is localized, tumor-specific immune activation while avoiding dose-limiting systemic toxicity.\"},{\"question\":\"What preclinical outcomes are reported for engineered Lactobacillus?\",\"answer\":\"The letter reports that IL-12–secreting L. plantarum can reduce colorectal tumor volume by up to 65%, TRAIL-expressing L. casei can reduce pancreatic tumor mass by about 40%, and IL-15–producing L. reuteri can enhance intratumoral CD8+ infiltration and improve survival in murine melanoma models.\"}]","Engineered Lactobacillus expressing tumor-killing cytokines - a novel biotherapeutic | PDF",1790674837]