[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-337837-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-337837-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","cancer-focus-personalized-cancer-t-cell-therapy-takes-the-stage-mirroring-vaccine-success","Cancer Focus - Personalized cancer T-cell therapy takes the stage, mirroring vaccine success","","Personalized cancer T-cell therapy is positioned as an emerging cornerstone of cancer care by tailoring cellular therapies to an individual’s genetic and antigenic profile, paralleling the success of personalized vaccines. The text compares cancer vaccine and T-cell therapy evolution, explains how tumor antigens are categorized as tumor-associated antigens and canonical neoantigens, and discusses the “dark matter” genome concept. It analyzes why TAAs face tolerance and limited precision while neoantigens drive stronger T-cell responses, then contrasts bulk and enriched strategies, highlighting shared hurdles like low immunogenicity, TCR affinity limits, and off-target toxicities.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/cancer-focus-personalized-cancer-t-cell-therapy-takes-the-stage-mirroring-vaccine-success/337837/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/cancer-focus-personalized-cancer-t-cell-therapy-takes-the-stage-mirroring-vaccine-success/337837.png","ImageObject",300,407,{"name":42,"@type":43},"Hazel","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",8,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How does personalized cancer T-cell therapy relate to personalized cancer vaccines?","Question",{"text":63,"@type":64},"TAAs are self-antigens present in healthy tissues, encountering central immune tolerance and lacking specificity for effective treatment. Neoantigens arise from genomic alterations, are unique to tumor cells, evade central tolerance, and tend to induce stronger T-cell responses due to higher avidity.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What strategy differences exist between whole-tumor lysate vaccines and neoantigen-focused approaches?",{"text":68,"@type":64},"Whole-tumor lysate strategies include many private antigens but show limited efficacy due to low expression levels and undefined antigen specificity. The text argues that targeting neoantigens can improve specificity and avidity, though challenges like limited immunogenicity and affinity constraints remain.",{"name":70,"@type":61,"acceptedAnswer":71},"Why do vaccines and T-cell therapies targeting shared antigens still have limited effectiveness?",{"text":72,"@type":64},"They can suffer from low immunogenicity or suboptimal TCR affinities, reducing efficacy. The text also notes off-target toxicities as an additional barrier, even when targeting antigens that may benefit larger patient groups.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},337837,1790123819,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":30,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":55},137441390410,"https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984","FOUND IN TRANSLATION  \nCancer Focus  \nPersonalized cancer T-cell therapy takes the stage, mirroring vaccine success  \nJohanna Chiffelle1,2,3 and Alexandre Harari1,2,3􀀁  \nPersonalized T-cell therapy is emerging as a pivotal treatment of cancer care by tailoring cellular therapies to individual genetic and antigenic profiles, echoing the exciting success of personalized vaccines. We describe here the parallel evolution and analogies of cancer vaccines and T-cell therapies.  \nIn cancer research, antigens have long been recognized as pivotal triggers of immune responses and potential therapeutic targets. Antigens are commonly categorized into tumor-associated antigens (TAAs) or canonical neoantigens (Peri et al., 2023). TAAs are selfantigens, showing varied expression patterns within tumors. They comprise tissue-specific antigens found exclusively in particular healthy tissues and in tumors, along with cancer germline antigens, which are typically silenced in most healthy tissues but become active again in cancerous cells (Peri et al., 2023). Due to their presence in healthy tissues, TAAs encounter central immune tolerance mechanisms and lack the specificity required for effective cancer treatment. On the contrary, canonical neoantigens, arising from genomic alterations, are unique to tumor cells and their offspring, evading central tolerance, and are being recognized as prototypic tumor rejection antigens. Recently, a new category of tumor antigens referred to as the “dark matter” of the genome has emerged (Peri et al., 2023). These encompass antigens resulting from non-canonical transcriptional and posttranscriptional aberrations in tumor cells, as well as those originating from intratumoral pathogens such as viruses, bacteria, or fungi. Antigens stemming from pathogens associated with cancer, such as Helicobacter pylori or  \nhuman papillomavirus, represent promising targets for cancer immunotherapy, while the role of other bacteria-derived antigens remains to be clarified (Peri et al., 2023).  \nUnlike canonical neoantigens, which are mostly private, TAAs are shared across various patients and cancer types, making them initially attractive but ultimately limited in their precision and effectiveness, leading to significant side effects (Peri et al., 2023). Lately, the greater clinical significance of neoantigens, when compared to TAAs, is attributed not only to their tumor-specific nature but also to the stronger T-cell responses they induce, owing to their superior avidity (Schmidt et al., 2023; Oliveira et al., 2021).  \nIn the cancer vaccine field, the initial strategy involving whole tumor lysate, including all private antigens, led to limited clinical efficacy due to low expression levels of variable and undefined antigenic specificity. By analogy, adoptive transfer of bulk tumor-infiltrating lymphocyte (TIL) products generated from individual patients offers complete patient specificity, although concomitant with an unpredictable and uncertain prevalence of tumor-specific clones (Chiffelle et al., 2023, Preprint) (Fig. 1 a) . In response to the latter limitations, more refined strategies have emerged. In the pursuit of personalized therapy, a fundamental objective is to  \nenrich treatment for tumor-specific responses, achieved by incorporating specific antigens into vaccines (Tanyi et al., 2018), mirroring the concept of enriched or selected TILs (Arnaud et al., 2022) (Fig. 1 b). Alternatively, the approach may focus exclusively on well-identified antigens (Hu et al., 2018), aligning with the core objective of T-cell receptor (TCR)-T/chimeric antigen receptorT-cell therapy (Chandran and Klebanoff, 2019)(Fig. 1 c). The success of this approach hinges heavily on the precise identification of tumor antigens and cognate TCRs, often centered around extensively studied shared TAAs. Nonetheless, even with the potential to benefita large group of patients, vaccines and T-cell therapies targeting these antigens face similar challenges, characterized by ","cbCaihkJczwKUgBQ","https://ap.wps.com/l/cbCaihkJczwKUgBQ","pdf",1146553,"English","# Personalized cancer T-cell therapy\n## Antigen categories and immune tolerance\n## Vaccine and T-cell therapy analogies and strategies","[{\"question\":\"How does personalized cancer T-cell therapy relate to personalized cancer vaccines?\",\"answer\":\"TAAs are self-antigens present in healthy tissues, encountering central immune tolerance and lacking specificity for effective treatment. Neoantigens arise from genomic alterations, are unique to tumor cells, evade central tolerance, and tend to induce stronger T-cell responses due to higher avidity.\"},{\"question\":\"What strategy differences exist between whole-tumor lysate vaccines and neoantigen-focused approaches?\",\"answer\":\"Whole-tumor lysate strategies include many private antigens but show limited efficacy due to low expression levels and undefined antigen specificity. The text argues that targeting neoantigens can improve specificity and avidity, though challenges like limited immunogenicity and affinity constraints remain.\"},{\"question\":\"Why do vaccines and T-cell therapies targeting shared antigens still have limited effectiveness?\",\"answer\":\"They can suffer from low immunogenicity or suboptimal TCR affinities, reducing efficacy. The text also notes off-target toxicities as an additional barrier, even when targeting antigens that may benefit larger patient groups.\"}]","Cancer Focus - Personalized cancer T-cell therapy takes the stage, mirroring vaccine success | PDF",1790020848]