Pub Date : 2026-01-21DOI: 10.1016/j.ymthe.2026.01.019
James Hugo Armstrong Clubb, Santeri Artturi Pakola, Sakari Joenväärä, Tatiana Viktorovna Kudling, Tiialotta Tohmola, Victor Arias, Elise Jirovec, Mirte van der Heijden, Dafne Carolina Alves Quixabeira, Annukka Pasanen, Lyna Haybout, Nea Ojala, Saru Basnet, Arianna Eleuteri, Julia Davila Ferrero, Stella Hirvenoja, Inge Marie Svane, Johanna Mäenpää, Katriina Jalkanen, Matthew Stephen Block, Tuomo Alanko, Tine Monberg, Sanae Zahraoui, Susanna Grönberg-Vähä-Koskela, Natasha Salmelin, Claudia Kistler, Riikka Havunen, Suvi Sorsa, João Manuel dos Santos, Victor Cervera-Carrascon, Anna Kanerva, Otto Hemminki, Risto Renkonen, Akseli Hemminki
{"title":"Dyslipidaemia-associated natural IgM improves oncolytic virus TILT-123 efficacy through antibody-dependent enhancement in solid tumours.","authors":"James Hugo Armstrong Clubb, Santeri Artturi Pakola, Sakari Joenväärä, Tatiana Viktorovna Kudling, Tiialotta Tohmola, Victor Arias, Elise Jirovec, Mirte van der Heijden, Dafne Carolina Alves Quixabeira, Annukka Pasanen, Lyna Haybout, Nea Ojala, Saru Basnet, Arianna Eleuteri, Julia Davila Ferrero, Stella Hirvenoja, Inge Marie Svane, Johanna Mäenpää, Katriina Jalkanen, Matthew Stephen Block, Tuomo Alanko, Tine Monberg, Sanae Zahraoui, Susanna Grönberg-Vähä-Koskela, Natasha Salmelin, Claudia Kistler, Riikka Havunen, Suvi Sorsa, João Manuel dos Santos, Victor Cervera-Carrascon, Anna Kanerva, Otto Hemminki, Risto Renkonen, Akseli Hemminki","doi":"10.1016/j.ymthe.2026.01.019","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.01.019","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"258 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014361","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 : 2026-01-21DOI: 10.1016/j.ymthe.2026.01.020
Yohei Kawai, Shin Kaneko
{"title":"Feeder-free generation of CD4 single-positive helper T cells from human iPSCs via stage-specific modulation of Notch and TCR Signaling","authors":"Yohei Kawai, Shin Kaneko","doi":"10.1016/j.ymthe.2026.01.020","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.01.020","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"63 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014320","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 : 2026-01-21DOI: 10.1016/j.ymthe.2026.01.017
Donovan Flumens, Diana Campillo-Davo, Florian Van Oers, Philip Anthony Gilbert Shaw, Eva Lion
{"title":"Strategies to eliminate native T cell receptors for adoptive T cell therapies","authors":"Donovan Flumens, Diana Campillo-Davo, Florian Van Oers, Philip Anthony Gilbert Shaw, Eva Lion","doi":"10.1016/j.ymthe.2026.01.017","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.01.017","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"213 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014294","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 : 2026-01-21DOI: 10.1016/j.ymthe.2026.01.024
Dawei Zou, Stephanie G. Yi, Yulin Dai, Luan Truong, Lillian W. Gaber, Richard L. Knight, Xiang Xiao, Rafik M. Ghobrial, Xian C. Li, Zhongming Zhao, Wenhao Chen, A.Osama Gaber
{"title":"CD8+ T cell differentiation into NK-like effector cells drives transplant rejection","authors":"Dawei Zou, Stephanie G. Yi, Yulin Dai, Luan Truong, Lillian W. Gaber, Richard L. Knight, Xiang Xiao, Rafik M. Ghobrial, Xian C. Li, Zhongming Zhao, Wenhao Chen, A.Osama Gaber","doi":"10.1016/j.ymthe.2026.01.024","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.01.024","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"85 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014301","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}
The disruption of vascular homeostasis is a key pathological feature of fundus abnormal vascular diseases, including wet age-related macular degeneration, diabetic macular edema, and retinal vein occlusion. While anti-vascular endothelial growth factor therapies are widely used, many patients exhibit limited or suboptimal responses. Through proteomic analysis of 173 aqueous humor samples from fundus abnormal vascular diseases patients, followed by validation in an independent cohort of 70 samples, this study identifies prosaposin as a potential therapeutic candidate. In vitro, prosaposin mitigated endothelial dysfunction and reduced vascular permeability, while in vivo, it demonstrated anti-angiogenic and anti-inflammatory effects comparable to aflibercept, effectively reducing vascular leakage and retinal edema. Additionally, prosaposin provided neuroprotection by preserving photoreceptor cells. These findings highlight prosaposin's dual role in maintaining vascular homeostasis and protecting neural tissues, suggesting its potential as an alternative treatment for patients unresponsive to anti- vascular endothelial growth factor therapies.
{"title":"Prosaposin is a Dual-Action Therapeutic Target for Vascular Stabilization and Neuroprotection.","authors":"Jianhao Bai,Sijie Li,Aiting Wang,Boqian Wang,Zhongqi Wan,Jiao Jiao Li,Yinghong Zhou,RenBing Jia,Haiying Jin,Peng Gao,Xianting Ding","doi":"10.1016/j.ymthe.2026.01.015","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.01.015","url":null,"abstract":"The disruption of vascular homeostasis is a key pathological feature of fundus abnormal vascular diseases, including wet age-related macular degeneration, diabetic macular edema, and retinal vein occlusion. While anti-vascular endothelial growth factor therapies are widely used, many patients exhibit limited or suboptimal responses. Through proteomic analysis of 173 aqueous humor samples from fundus abnormal vascular diseases patients, followed by validation in an independent cohort of 70 samples, this study identifies prosaposin as a potential therapeutic candidate. In vitro, prosaposin mitigated endothelial dysfunction and reduced vascular permeability, while in vivo, it demonstrated anti-angiogenic and anti-inflammatory effects comparable to aflibercept, effectively reducing vascular leakage and retinal edema. Additionally, prosaposin provided neuroprotection by preserving photoreceptor cells. These findings highlight prosaposin's dual role in maintaining vascular homeostasis and protecting neural tissues, suggesting its potential as an alternative treatment for patients unresponsive to anti- vascular endothelial growth factor therapies.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"52 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005161","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 : 2026-01-20DOI: 10.1016/j.ymthe.2026.01.016
Sunetra Sase, Julia L. Hacker, Prabhat R. Napit, Anjali Bhagavatula, Sarah Woidill, Annemarie D’Alessandro, Marisa A. Jeffries, Akshata Almad, Asako Takanohashi, Quasar S. Padiath, Judith B. Grinspan, Eric D. Marsh, Adeline Vanderver
{"title":"Therapeutic suppression of Tubb4a rescues H-ABC leukodystrophy.","authors":"Sunetra Sase, Julia L. Hacker, Prabhat R. Napit, Anjali Bhagavatula, Sarah Woidill, Annemarie D’Alessandro, Marisa A. Jeffries, Akshata Almad, Asako Takanohashi, Quasar S. Padiath, Judith B. Grinspan, Eric D. Marsh, Adeline Vanderver","doi":"10.1016/j.ymthe.2026.01.016","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.01.016","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"26 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014317","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 : 2026-01-14DOI: 10.1016/j.ymthe.2026.01.003
Hongzhi Zeng, Aidi Liu, Tyler C. Daniel, Devin A. Golla, Zhenyu Lu, Rebecca Serodio, Brigid A. Millette, Ananya Lingineni, Peretz Gilberd, Kelly Chee, Komal Talloo, Advaith Peddi, So Hyun Park, Gang Bao, Xue Gao
{"title":"Precision A3G Base Editors for Disease Modeling and Correction","authors":"Hongzhi Zeng, Aidi Liu, Tyler C. Daniel, Devin A. Golla, Zhenyu Lu, Rebecca Serodio, Brigid A. Millette, Ananya Lingineni, Peretz Gilberd, Kelly Chee, Komal Talloo, Advaith Peddi, So Hyun Park, Gang Bao, Xue Gao","doi":"10.1016/j.ymthe.2026.01.003","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.01.003","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"55 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962411","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 : 2026-01-10DOI: 10.1016/j.ymthe.2026.01.001
Gabriel A Barragán Bravo,David A de la Cerda,Elisa Landoni,Kshiti Dholakia,Piotr Humeniuk,Leidy D Caraballo Galva,Ying Wang,Gengwen Tian,Boning Yang,Linjie Guo,Michael S Wood,Xavier Rios,Xin Xu,Amy N Courtney,Erica J Di Pierro,Joan Jacob,Yi-Han Li,Akshaya Adaikkalavan,Norihiro Watanabe,Sufeng Mao,George Miles,Gianpietro Dotti,Leonid S Metelitsa
Invariant natural killer T cells (NKTs) have intrinsic anti-tumor properties that make them promising candidates for chimeric antigen receptor (CAR) immunotherapies. Transgenic cytokine expression can enhance cellular therapy potency, and we hypothesized that co-expressing IL-18 alone or with IL-15 would boost CAR-NKT therapeutic potential. To test this, we generated retroviral constructs expressing IL-15 and/or IL-18 with an inducible caspase 9 safety switch and co-transduced them with a GD2-specific CAR into human NKTs. Co-expression of IL-18 or IL-15/IL-18 increased CAR-NKT cytotoxicity, proliferation, and cytokine secretion in vitro compared to IL-15 alone. IL-18 also enhanced GPC3.CAR and CD19.CAR NKT activity against hepatocellular carcinoma and B cell leukemia cells, respectively. In a metastatic neuroblastoma model, IL-18-expressing GD2.CAR-NKTs controlled tumors more effectively than IL-15-only cells, but mice in the IL-15/IL-18 group developed severe toxicities not observed in the IL-18-only group. Mechanistically, IL-18 induced a transcriptional program distinct from IL-15, marked by lower exhaustion signatures and enrichment of metabolic pathways. Finally, targeted metabolomics showed that IL-18 drives broad metabolic reprogramming in CAR-NKTs including increased oxidative phosphorylation, glycolysis, glutaminolysis, and purine metabolism. These findings support the use of IL-18 in developing the next generation of cytokine-armed CAR-NKT cancer immunotherapies.
{"title":"IL-18 metabolically reprograms CAR-expressing natural killer T cells and enhances their antitumor activity.","authors":"Gabriel A Barragán Bravo,David A de la Cerda,Elisa Landoni,Kshiti Dholakia,Piotr Humeniuk,Leidy D Caraballo Galva,Ying Wang,Gengwen Tian,Boning Yang,Linjie Guo,Michael S Wood,Xavier Rios,Xin Xu,Amy N Courtney,Erica J Di Pierro,Joan Jacob,Yi-Han Li,Akshaya Adaikkalavan,Norihiro Watanabe,Sufeng Mao,George Miles,Gianpietro Dotti,Leonid S Metelitsa","doi":"10.1016/j.ymthe.2026.01.001","DOIUrl":"https://doi.org/10.1016/j.ymthe.2026.01.001","url":null,"abstract":"Invariant natural killer T cells (NKTs) have intrinsic anti-tumor properties that make them promising candidates for chimeric antigen receptor (CAR) immunotherapies. Transgenic cytokine expression can enhance cellular therapy potency, and we hypothesized that co-expressing IL-18 alone or with IL-15 would boost CAR-NKT therapeutic potential. To test this, we generated retroviral constructs expressing IL-15 and/or IL-18 with an inducible caspase 9 safety switch and co-transduced them with a GD2-specific CAR into human NKTs. Co-expression of IL-18 or IL-15/IL-18 increased CAR-NKT cytotoxicity, proliferation, and cytokine secretion in vitro compared to IL-15 alone. IL-18 also enhanced GPC3.CAR and CD19.CAR NKT activity against hepatocellular carcinoma and B cell leukemia cells, respectively. In a metastatic neuroblastoma model, IL-18-expressing GD2.CAR-NKTs controlled tumors more effectively than IL-15-only cells, but mice in the IL-15/IL-18 group developed severe toxicities not observed in the IL-18-only group. Mechanistically, IL-18 induced a transcriptional program distinct from IL-15, marked by lower exhaustion signatures and enrichment of metabolic pathways. Finally, targeted metabolomics showed that IL-18 drives broad metabolic reprogramming in CAR-NKTs including increased oxidative phosphorylation, glycolysis, glutaminolysis, and purine metabolism. These findings support the use of IL-18 in developing the next generation of cytokine-armed CAR-NKT cancer immunotherapies.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"3 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947414","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：