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The study develops rBCG-LTAK63, a recombinant BCG strain, and evaluates it in vitro and in vivo. In cell co-cultures, rBCG enhances T cell activation and improves spheroid growth control. In mouse models, rBCG reduces implanted tumor growth, promotes systemic CD4+ and CD8+ T cell activation, and strengthens NK and dendritic cell activation. It increases tumor immune infiltration, boosts CD8+ T cell and dendritic cell activation, and decreases regulatory T cell frequency, sustaining a less immunosuppressive microenvironment and showing translational potential in an orthotopic model.",{"@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/rbcg-ltak63-outperforms-bcg-in-bladder-cancer-immunotherapy-dendritic-and-t-cell-coordination-drives-superior-tumor-control-in-a-mouse-model/458453/",{"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/rbcg-ltak63-outperforms-bcg-in-bladder-cancer-immunotherapy-dendritic-and-t-cell-coordination-drives-superior-tumor-control-in-a-mouse-model/458453.png","ImageObject",300,407,{"name":92,"@type":93},"Putri","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does rBCG-LTAK63 aim to address in NMIBC?","Question",{"text":112,"@type":113},"BCG is effective for NMIBC, but around 30% of patients fail to respond, develop resistance, and experience tumor recurrence. rBCG-LTAK63 is designed to improve immunotherapeutic efficacy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does rBCG-LTAK63 perform compared with conventional BCG in vitro?",{"text":117,"@type":113},"In MB49 cell/splenocyte co-cultures, rBCG outperforms BCG by enhancing T cell activation and improving spheroid growth control.",{"name":119,"@type":110,"acceptedAnswer":120},"What immune changes does rBCG-LTAK63 induce in vivo?",{"text":121,"@type":113},"rBCG uniquely promotes systemic activation of CD4+ and CD8+ T cells and strengthens activation of NK and dendritic cells in the spleen, while within tumors it increases immune infiltration, enhances CD8+ T cell and dendritic cell activation, and reduces regulatory T cells to lessen immunosuppression.","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},458453,1790820453,{"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":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"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,"preview_page_count":4},962085571259,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Ivyspring  \nInternational Publisher  \nInternationalJournal of Biological Sciences  \n2026; 22(2): 713-730. doi: 10.7150/ijbs.118329  \nResearch Paper  \nrBCG-LTAK63 Outperforms BCG in Bladder Cancer Immunotherapy: Dendritic and T Cell Coordination Drives Superior Tumor Control in a Mouse Model  \nMatheus Ferreira de Almeida1\\#, Bruna Gennari Rosa1\\#, Daniela Delechiave1, Lucas Francisco Annequin1,2, Lazaro Moreira Marques-Neto1, Monalisa Martins Trentini1, Johanna Christine van Vliet1, Isabelle Carolina Cotrim Gozzi1, Ana Carolina de Oliveira Carvalho1, Dunia Rodriguez1, Lennon Ramos Pereira1, Giana Carla Gaboardi1, Luís Carlos de Souza Ferreira3, Luciana Cezar de Cerqueira Leite1􀀍, Ana Carolina Ramos Moreno1,3􀀍  \n1. Vaccine Development Laboratory, Butantan Institute, São Paulo, SP, Brazil.  \n2. Université Claude Bernard Lyon 1, Lyon, France.  \n3. Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.  \n\\#Both authors contributed equally.  \n􀀍 Corresponding authors: Ana Carolina Ramos Moreno: ana.moreno@butantan.gov.br; Luciana Cezar de Cerqueira Leite: [luciana.leite@butantan.gov.br](luciana.leite@butantan.gov.br).  \n© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions.  \nReceived: 2025.05.27; Accepted: 2025.10.11; Published: 2026.01.01  \nAbstract  \nBacillus Calmette-Guérin (BCG) remains the standard treatment for non-muscle invasive bladder cancer (NMIBC), yet approximately 30% of patients fail to respond. To enhance therapeutic efficacy, we developed rBCG-LTAK63, a recombinant BCG strain, as a novel immunotherapeutic candidate. In vitro, rBCG outperformed BCG in MB49 cell/splenocyte co-cultures by enhancing T cell activation and improving spheroid growth control. In vivo, rBCG demonstrated superior antitumor efficacy, significantly reducing the growth of subcutaneously implanted MB49 tumor cells. Immune profiling revealed that rBCG uniquely promoted systemic activation of both CD4⁺ and CD8⁺ T cells, alongside stronger activation of NK and dendritic cells in the spleen. Within the tumor microenvironment, rBCG increased immune cell infiltration, enhanced activation of CD8⁺ T cells and dendritic cells, and decreased the frequency of regulatory T cells, fostering a less immunosuppressive environment. Unlike parental BCG, rBCG-LTAK63 sustained a potent immunostimulatory profile, marked by robust activation of dendritic cells and effector T cells. Similar results were also observed in the orthotopic model, suggesting a translational potential of rBCG-LTAK63. Collectively, our findings demonstrate that rBCG outperforms conventional BCG and represents a promising strategy for improving NMIBC treatment.  \nKeywords: BCG, recombinant BCG, bladder cancer, immune response, immunotherapy  \nIntroduction  \nBladder cancer is a malignant neoplasia of the urinary system, accounting for over 90% of all urothelial tumors (1) . According to the International Agency for Research on Cancer (IARC), bladder cancer ranks as the eleventh most common malignancy worldwide. In 2022, approximately 600,000 new cases were diagnosed, and more than 220,000 deaths were attributed to this disease globally, emphasizing the critical need for ongoing research in  \nthis domain. Upon diagnosis of bladder cancer, it is imperative to ascertain the location and extent of tumor cell growth, particularly whether there is muscular invasion. In its early stages, when confined to the bladder lining, the cancer is classified as non-muscle invasive bladder cancer (NMIBC), comprising about 70% of diagnosed cases (2,3) . Conversely, in advanced stages, where cancer penetrates the muscular wall, it is classified as  \nmuscle-invasive bladder cancer (MIBC), accounting for 30% of c","cbCaipCwdNIzn8F1","https://ap.wps.com/l/cbCaipCwdNIzn8F1","pdf",8294300,18,"English","# Abstract\n# Introduction","[{\"question\":\"What problem does rBCG-LTAK63 aim to address in NMIBC?\",\"answer\":\"BCG is effective for NMIBC, but around 30% of patients fail to respond, develop resistance, and experience tumor recurrence. rBCG-LTAK63 is designed to improve immunotherapeutic efficacy.\"},{\"question\":\"How does rBCG-LTAK63 perform compared with conventional BCG in vitro?\",\"answer\":\"In MB49 cell/splenocyte co-cultures, rBCG outperforms BCG by enhancing T cell activation and improving spheroid growth control.\"},{\"question\":\"What immune changes does rBCG-LTAK63 induce in vivo?\",\"answer\":\"rBCG uniquely promotes systemic activation of CD4+ and CD8+ T cells and strengthens activation of NK and dendritic cells in the spleen, while within tumors it increases immune infiltration, enhances CD8+ T cell and dendritic cell activation, and reduces regulatory T cells to lessen immunosuppression.\"}]","rBCG-LTAK63 Outperforms BCG in Bladder Cancer Immunotherapy - Dendritic and T Cell Coordination Drives Superior Tumor Control in a Mouse Model | PDF",1790753171,45]