Pub Date : 2026-02-06DOI: 10.1016/j.ymthe.2026.02.006
Isabella Elias Yonezawa Ogusuku, Nele Knelangen, Boris Engels, Marion Subklewe, Dominik Lock
{"title":"Mapping the clinical landscape of multifunctional CAR T cells: targets, trends, and synergies","authors":"Isabella Elias Yonezawa Ogusuku, Nele Knelangen, Boris Engels, Marion Subklewe, Dominik Lock","doi":"10.1016/j.ymthe.2026.02.006","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.02.006","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"17 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146134062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1016/j.ymthe.2026.02.005
Apolonia Gardner, Shuai Wang, Adam Daniels, Dan Li, Christine Wu, Lucas Lin, Christin Hong, Sophia R. Zhao, Kamil Kruczek, Genevieve Weist, Laura Barrio Real, Joan Wicks, Mohamad Nayal, Ashley Carter, Christine Ott, Virginia Haurigot, Richard T. Born, Constance L. Cepko
{"title":"AAV NRF2 Gene Therapy Preserves Retinal Structure and Function in Rodent Models of Oxidative Damage","authors":"Apolonia Gardner, Shuai Wang, Adam Daniels, Dan Li, Christine Wu, Lucas Lin, Christin Hong, Sophia R. Zhao, Kamil Kruczek, Genevieve Weist, Laura Barrio Real, Joan Wicks, Mohamad Nayal, Ashley Carter, Christine Ott, Virginia Haurigot, Richard T. Born, Constance L. Cepko","doi":"10.1016/j.ymthe.2026.02.005","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.02.005","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"39 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146134064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1016/j.ymthe.2026.02.001
Adeel Saleem, Qi Peng, Ziqin Tang, Yasmin R. Mohseni, Cristiano Scottà, Panicos Shangaris, Kimberly Smit, Wilbert P. Vermeij, Fadi Issa, Giovanna Lombardi, Gilbert O. Fruhwirth
{"title":"CAR-mediated release of IL-10 increases the function of regulatory T cells: relevance for future clinical application","authors":"Adeel Saleem, Qi Peng, Ziqin Tang, Yasmin R. Mohseni, Cristiano Scottà, Panicos Shangaris, Kimberly Smit, Wilbert P. Vermeij, Fadi Issa, Giovanna Lombardi, Gilbert O. Fruhwirth","doi":"10.1016/j.ymthe.2026.02.001","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.02.001","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"30 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146134067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-05DOI: 10.1016/j.ymthe.2026.01.043
Eunhye Kim, Yeonsoo Yang, Solchan Won, Namhee Lee, Young-In Kim, Suk-Kyung Shin, Songyi Lee, Mi-Ju Park, Hang-Rae Kim, Keunhee Oh, Dong-Sup Lee
Oncolytic viruses offer promising immunotherapy for cancer but face challenges such as delivery, targeting, and immune clearance. Our prior work showed that vaccinia virus (VACV) displaying the complement regulator CD55 evaded complement-mediated clearance, enhancing delivery and targeting in xenograft models. Importantly, this modified VACV also escaped neutralizing antibodies (NAbs) in vitro, a finding with significant implications. To improve translational relevance, we independently evaluated NAb evasion in immunocompetent in vivo models and against human-derived NAbs. Our novel platform virus, SJ-650-a CD55-displaying VACV expressing murine GM-CSF-retained superior antitumor efficacy despite the presence of NAbs in syngeneic breast cancer models. Additionally, SJ-650 effectively evaded NAbs derived from the serum of a clinical VACV trial (REN026). NAb evasion was CD55-dependent, occurred independently of complement activity, and was mediated by steric hindrance via the extracellular CD55 motif. NAb pretreatment masked binding of the key viral entry proteins A27, L1, and H3 in control viruses lacking CD55, but these interactions remained intact in SJ-650. By circumventing both complement and antibody responses, SJ-650 significantly inhibited tumor growth in two metastasis models, inducing immunogenic cell death and reprogramming the tumor microenvironment. These findings support SJ-650's potential as a robust oncolytic platform with broad translational applicability.
{"title":"CD55-displaying oncolytic vaccinia virus treated metastatic cancers by evading the effect of host innate and adaptive humoral responses.","authors":"Eunhye Kim, Yeonsoo Yang, Solchan Won, Namhee Lee, Young-In Kim, Suk-Kyung Shin, Songyi Lee, Mi-Ju Park, Hang-Rae Kim, Keunhee Oh, Dong-Sup Lee","doi":"10.1016/j.ymthe.2026.01.043","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.01.043","url":null,"abstract":"<p><p>Oncolytic viruses offer promising immunotherapy for cancer but face challenges such as delivery, targeting, and immune clearance. Our prior work showed that vaccinia virus (VACV) displaying the complement regulator CD55 evaded complement-mediated clearance, enhancing delivery and targeting in xenograft models. Importantly, this modified VACV also escaped neutralizing antibodies (NAbs) in vitro, a finding with significant implications. To improve translational relevance, we independently evaluated NAb evasion in immunocompetent in vivo models and against human-derived NAbs. Our novel platform virus, SJ-650-a CD55-displaying VACV expressing murine GM-CSF-retained superior antitumor efficacy despite the presence of NAbs in syngeneic breast cancer models. Additionally, SJ-650 effectively evaded NAbs derived from the serum of a clinical VACV trial (REN026). NAb evasion was CD55-dependent, occurred independently of complement activity, and was mediated by steric hindrance via the extracellular CD55 motif. NAb pretreatment masked binding of the key viral entry proteins A27, L1, and H3 in control viruses lacking CD55, but these interactions remained intact in SJ-650. By circumventing both complement and antibody responses, SJ-650 significantly inhibited tumor growth in two metastasis models, inducing immunogenic cell death and reprogramming the tumor microenvironment. These findings support SJ-650's potential as a robust oncolytic platform with broad translational applicability.</p>","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.0,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-04Epub Date: 2026-01-07DOI: 10.1016/j.ymthe.2025.12.051
Allison M Bradbury
{"title":"Navigating new horizons: Key insights from ASGCT's 2025 Policy Summit.","authors":"Allison M Bradbury","doi":"10.1016/j.ymthe.2025.12.051","DOIUrl":"10.1016/j.ymthe.2025.12.051","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":"650-652"},"PeriodicalIF":12.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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