Molecular Therapy最新文献

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GDF11: A promising new drug target for pulmonary fibrosis? GDF11:治疗肺纤维化的新药物靶点?
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-19 DOI: 10.1016/j.ymthe.2025.09.016
Gaetano Caramori,Francesca Rossi,Ian M Adcock
{"title":"GDF11: A promising new drug target for pulmonary fibrosis?","authors":"Gaetano Caramori,Francesca Rossi,Ian M Adcock","doi":"10.1016/j.ymthe.2025.09.016","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.016","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"7 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093492","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}
引用次数: 0
Clinical prospects of oncolytic viruses: Key developments and challenges. 溶瘤病毒的临床前景:关键进展和挑战。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-17 DOI: 10.1016/j.ymthe.2025.09.002
Zijun Wang,Yinan Shen,Tingbo Liang
{"title":"Clinical prospects of oncolytic viruses: Key developments and challenges.","authors":"Zijun Wang,Yinan Shen,Tingbo Liang","doi":"10.1016/j.ymthe.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.002","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"11 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083393","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}
引用次数: 0
Correction of von Willebrand factor multimerization in type 2A/ⅡC von Willebrand disease by exogenous VWF propeptide supplementation. 外源性VWF前肽补充对2A/ⅡC型血管性血友病血管性血友病因子多聚合的纠正作用
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-16 DOI: 10.1016/j.ymthe.2025.09.027
Ziqi Zhang,Qian Liang,Xiaoqian Xu,Yang Li,Changming Chen,Qiulan Ding,Aiwu Zhou,Wenman Wu,Xuefeng Wang,Jing Dai
{"title":"Correction of von Willebrand factor multimerization in type 2A/ⅡC von Willebrand disease by exogenous VWF propeptide supplementation.","authors":"Ziqi Zhang,Qian Liang,Xiaoqian Xu,Yang Li,Changming Chen,Qiulan Ding,Aiwu Zhou,Wenman Wu,Xuefeng Wang,Jing Dai","doi":"10.1016/j.ymthe.2025.09.027","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.027","url":null,"abstract":"Gene therapy remains the only cure for von Willebrand disease (VWD), but is limited by the large von Willebrand factor (VWF) gene size. Variants affecting the VWF propeptide (VWFpp) impair multimerization, causing type 2A/IIC VWD. VWFpp serves as a pH-sensitive template for VWF multimer assembly, suggesting that in trans VWFpp supplementation may restore multimerization in VWF variants with defective propeptides. Co-expression of wild-type VWFpp with mutant full-length VWF in vitro led to modest yet consistent improvements in the VWF multimer profile across eight type 2A/IIC VWD-causing variants. Notably, variants with defect D2:D2 interface required lower levels of VWFpp for multimerization rescue, whereas those with intact D2:D2 interfaces exhibited a greater demand. Futhermore a transgenic mouse model of type 2A/IIC VWD carrying the p.Tyr87Ser mutation was treated with an AAV9 vector encoding VWFpp under the control of endothelial-specific promoters. VWFpp administration remarkably restored VWF multimerization, increased the VWF:CB levels from 15.8±10.2% to 71.2±12.7% for at least 16 weeks, corrected the bleeding tendency and improved platelet function. Both in vitro and in vivo findings demonstrate that in trans VWFpp supplementation can rectify defects in VWF multimerization caused by variants in VWFpp, offering a novel therapeutic strategy for type 2A/IIC VWD.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"18 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071731","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}
引用次数: 0
Epigenetic Mechanisms of HIV and Opioid-Induced Neuropathology: Potential Therapies and Interventions. HIV和阿片类药物诱导的神经病理的表观遗传机制:潜在的治疗和干预。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-16 DOI: 10.1016/j.ymthe.2025.09.028
Florida Owens,Candy Carbajal,Myosotys Rodriguez,Nazira El-Hage
{"title":"Epigenetic Mechanisms of HIV and Opioid-Induced Neuropathology: Potential Therapies and Interventions.","authors":"Florida Owens,Candy Carbajal,Myosotys Rodriguez,Nazira El-Hage","doi":"10.1016/j.ymthe.2025.09.028","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.028","url":null,"abstract":"HIV continues to be a significant global health issue, especially regarding its connection to the opioid epidemic. Substance abuse heightens the risk of spreading HIV infection and is linked to treatment non-compliance, accelerated disease progression, and increased mortality. Recent studies link epigenetic changes with the emergence of opioid addiction and neurodegenerative diseases. Despite new insights, the lasting epigenetic effects of opioid abuse on the severity, progression, and outlook of HIV-associated neurocognitive disorders (HAND) remain unclear. HAND occurs even with adequate antiretroviral therapy, for which there are currently no effective treatments. The epigenome in the central nervous system (CNS) plays a crucial role in helping humans adapt to a changing environment, and its dysregulation can lead to various CNS disorders; however, the underlying mechanisms of such developments are poorly understood. At present, several epigenetic drugs are being developed and tested in clinical trials as supplemental therapies for CNS disorders, including age-related neurodegeneration, mood disorders, and behavioral disorders. Accumulated evidence suggests that future therapeutic strategies should prioritize the development of epigenetic drugs, or epidrugs, as adjunct therapies for treating CNS disorders, including HAND and addiction-related diseases. This review explores the epigenetic mechanisms governing HIV-related neurological impairment amid the influence of opioid abuse.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"73 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071732","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}
引用次数: 0
Adoptive transfer of NK cells engineered with a CD5-based chimeric antigen receptor (SRCD5CAR) to treat invasive fungal infections. 用基于cd5的嵌合抗原受体(SRCD5CAR)工程NK细胞过继转移治疗侵袭性真菌感染
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-16 DOI: 10.1016/j.ymthe.2025.09.003
María Velasco-de Andrés,Cristina Català,Laura Carrillo-Serradell,Violeta Planells-Romeo,Lucía Aragón-Serrano,Marta Español-Rego,Lorena Pérez-Amill,Pedro Puerta-Alcalde,Carolina García-Vidal,Manel Juan,Beatriz Martín-Antonio,Francisco Lozano
{"title":"Adoptive transfer of NK cells engineered with a CD5-based chimeric antigen receptor (SRCD5CAR) to treat invasive fungal infections.","authors":"María Velasco-de Andrés,Cristina Català,Laura Carrillo-Serradell,Violeta Planells-Romeo,Lucía Aragón-Serrano,Marta Español-Rego,Lorena Pérez-Amill,Pedro Puerta-Alcalde,Carolina García-Vidal,Manel Juan,Beatriz Martín-Antonio,Francisco Lozano","doi":"10.1016/j.ymthe.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.003","url":null,"abstract":"The treatment of invasive fungal infections (IFI) poses a major health challenge due to their severity, the scarcity and toxicity of current antifungal drugs, and the emergence of drug-resistant strains, thus forcing the search for novel strategies. Approaches involving adoptive transfer of immune cells harboring chimeric antigen receptors (CARs) are gaining momentum in several clinical settings. Based on the fungal β-glucan-binding properties of the lymphocyte scavenger receptor CD5, we assayed NK and T cells engineered with a CD5-based second generation CAR (SRCD5CAR) for the treatment of IFI. In vitro results revealed that SRCD5CAR expression specifically potentiates NK cell activation (i.e., CD69 expression and cytokine/chemokine production) and killing (i.e., CD107a expression and perforin/granzyme production) against different pathogenic fungal species (i.e., Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus and Fusarium solani). Further in vivo infusion of SRCD5CAR-NK cells into fungal-infected NSG mice increased survival rates and decreased fungal burden in target organs. Similar in vitro and in vivo anti-fungal observations were also obtained for SRCD5CAR-T cells. Overall, the superior and specific performance exhibited by SRCD5CAR-transduced NK cells open new avenues for the development of novel off-the-shelf adoptive transfer of allogeneic cells against IFI, be those alone or adjunctive to antifungal drugs.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"15 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078124","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}
引用次数: 0
Telomerase mRNA Therapy Protects Human Skin Against Radiation-Induced DNA Damage. 端粒酶mRNA治疗保护人体皮肤免受辐射诱导的DNA损伤。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-16 DOI: 10.1016/j.ymthe.2025.09.029
Shuang Li,David F Chang,Karem A Court,Thi Kim Cuc Nguyen,Vrutant V Shah,Elisa Morales,Jack Carrier,Anjana Tiwari,Andrew T Ludlow,Kristopher W Brannan,Aldona J Spiegel,Maham Rahimi,Jeffrey D Friedman,Elizabeth Olmsted-Davis,Biana Godin,Anahita Mojiri,John P Cooke
{"title":"Telomerase mRNA Therapy Protects Human Skin Against Radiation-Induced DNA Damage.","authors":"Shuang Li,David F Chang,Karem A Court,Thi Kim Cuc Nguyen,Vrutant V Shah,Elisa Morales,Jack Carrier,Anjana Tiwari,Andrew T Ludlow,Kristopher W Brannan,Aldona J Spiegel,Maham Rahimi,Jeffrey D Friedman,Elizabeth Olmsted-Davis,Biana Godin,Anahita Mojiri,John P Cooke","doi":"10.1016/j.ymthe.2025.09.029","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.029","url":null,"abstract":"Radiation therapy, while effective against cancer, often causes collateral damage to surrounding healthy tissues, leading to DNA damage that can precipitate genomic instability and cancer. Despite the enormity of the problem, there is currently no FDA-approved agent to prevent or treat skin damage caused by ionizing radiation. In the current study, ionizing radiation induced dose-dependent genomic and mitochondrial DNA damage, leading to apoptosis in primary cutaneous cells. Prior treatment with mRNA encoding telomerase reverse transcriptase (TERT) substantially reduced radiation induced DNA damage in human primary skin cells and tissues. Mechanistically, TERT mRNA pretreatment enhances DNA repair through the homologous recombination pathway, reduces mitochondrial ROS, and decreases apoptosis without extending telomere length during the experimental period, suggesting a non-canonical function of TERT to accelerate cellular recovery from radiation. These findings highlight a potential therapeutic approach for preventing radiation-induced skin injury.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"22 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071853","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}
引用次数: 0
Melanocortins: A new paradigm in immunotherapy for membranous nephropathy. 黑素皮质素:膜性肾病免疫治疗的新范例。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-13 DOI: 10.1016/j.ymthe.2025.08.054
Yuan Gui,Dong Zhou
{"title":"Melanocortins: A new paradigm in immunotherapy for membranous nephropathy.","authors":"Yuan Gui,Dong Zhou","doi":"10.1016/j.ymthe.2025.08.054","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.08.054","url":null,"abstract":"","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"20 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058947","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}
引用次数: 0
Exploring the role of readthrough-inducing molecule 2,6-diaminopurine to increase immune response against cancer cells. 探索读透诱导分子2,6-二氨基嘌呤在增强对癌细胞免疫应答中的作用。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-12 DOI: 10.1016/j.ymthe.2025.09.024
Carmen Sandoval Pacheco,Alice M Leroy,Mehdi Derhourhi,Tristan Cardon,Catherine Leroy,Nathalie Jouy,Emmanuelle Com,Blandine Guevel,Roland Bourette,Julie Carrard,Daniela Barros,Belinda Duchêne,Bénédicte Toussaint,Philippe Froguel,Nicolas Jonckheere,Thierry Chassat,Isabelle Van Seuningen,Régis Lavigne,Charles Pineau,Philippe Pierre,Fabrice Soncin,Michel Salzet,Amélie Bonnefond,Fabrice Lejeune
{"title":"Exploring the role of readthrough-inducing molecule 2,6-diaminopurine to increase immune response against cancer cells.","authors":"Carmen Sandoval Pacheco,Alice M Leroy,Mehdi Derhourhi,Tristan Cardon,Catherine Leroy,Nathalie Jouy,Emmanuelle Com,Blandine Guevel,Roland Bourette,Julie Carrard,Daniela Barros,Belinda Duchêne,Bénédicte Toussaint,Philippe Froguel,Nicolas Jonckheere,Thierry Chassat,Isabelle Van Seuningen,Régis Lavigne,Charles Pineau,Philippe Pierre,Fabrice Soncin,Michel Salzet,Amélie Bonnefond,Fabrice Lejeune","doi":"10.1016/j.ymthe.2025.09.024","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.024","url":null,"abstract":"Immuno-oncotherapy is a highly promising therapeutic strategy that relies on the ability of cancer cells to present specific antigenic epitopes at their surfaces. Because they proliferate rapidly, cancer cells frequently accumulate genetic variants, including premature termination codons. In this study, we investigated the potential of 2,6-diaminopurine (DAP), a potent translational-readthrough-inducing molecule, to elicit an antitumor immune response. Readthrough-resulting proteins following DAP treatment can be displayed at the cell surface by the major histocompatibility complex, thus potentially enhancing immune recognition. This was demonstrated using a construct encoding firefly luciferase interrupted by a UGA stop codon and fused at its C-terminus with the SL8 antigenic peptide. Furthermore, in vivo exposure to DAP promotes recruitment of immune effector cells, including T lymphocytes, macrophages, and natural killer cells, to the tumor microenvironment. These findings suggest that DAP and potentially, other translational readthrough-inducing molecules hold promise as novel candidate drugs for antitumor therapy.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"19 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056677","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}
引用次数: 0
Harnessing mRNA-encoded PcrV-targeting monoclonal antibodies for combating antibiotic-resistant Pseudomonas aeruginosa infections. 利用mrna编码pcrv靶向单克隆抗体对抗耐药铜绿假单胞菌感染。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-12 DOI: 10.1016/j.ymthe.2025.09.025
Xingyun Wang,Xingyue Gao,Cong Liu,Liang Yang,Liang Li,Nino Rcheulishvili,Ziqian Wang,Jiubiao Guo,Chuanlan Yang,Yueling Zheng,Xuehua Pan,Peng George Wang,Yunjiao He
{"title":"Harnessing mRNA-encoded PcrV-targeting monoclonal antibodies for combating antibiotic-resistant Pseudomonas aeruginosa infections.","authors":"Xingyun Wang,Xingyue Gao,Cong Liu,Liang Yang,Liang Li,Nino Rcheulishvili,Ziqian Wang,Jiubiao Guo,Chuanlan Yang,Yueling Zheng,Xuehua Pan,Peng George Wang,Yunjiao He","doi":"10.1016/j.ymthe.2025.09.025","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.025","url":null,"abstract":"The rising prevalence of antibiotic resistance, particularly among Pseudomonas aeruginosa strains, has become a substantial threat to public health. There is an urgent need for new therapeutics to tackle this challenge. This study explores the potential of mRNA-encoded monoclonal antibodies (mAbs) targeting the type III secretion system protein V (PcrV) antigen as a strategy to combat P. aeruginosa infections. We derived anti-PcrV mAbs from the B cells of immunized mice and identified two potent monoclonal antibodies (mAbs), M2C10 and M4C12 with the strongest binding affinity to PcrV. These mAbs were expressed, purified to high homogeneity, and encoded into mRNA for in vitro and in vivo functional assays. The results indicated that both mAbs exhibit high antibacterial activity in vitro. For in vivo efficacy, specific pathogen-free male BALB/c mice were used in acute systemic and pneumonia models. Survival, tissue bacterial loads, and histopathology were assessed. M2C10-mRNA outperformed M4C12-mRNA in increasing the survival rate of challenged mice, reducing tissue bacterial loads, and protecting against tissue damage in a murine model of acute infection. Collectively, our findings indicate that mRNA-encoded mAbs, particularly M2C10, offer a promising therapeutic strategy against P. aeruginosa, potentially serving as an alternative to conventional antibiotics and warrant further exploration.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"64 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056679","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}
引用次数: 0
Allogeneic stem cell-engineered EGFRvIII-specific CAR-NKT cells for treating glioblastoma with enhanced efficacy and safety. 同种异体干细胞工程的egfrviii特异性CAR-NKT细胞治疗胶质母细胞瘤的有效性和安全性增强。
IF 12.4 1区 医学
Molecular Therapy Pub Date : 2025-09-12 DOI: 10.1016/j.ymthe.2025.09.026
Yan-Ruide Li,Yichen Zhu,Zhe Li,Xinyuan Shen,Tyler Halladay,Christopher Tse,Yanxin Tian,Jie Huang,Annabel S Zhao,Nathan Y Ma,Catherine Zhang,David A Nathanson,Robert M Prins,Lili Yang
{"title":"Allogeneic stem cell-engineered EGFRvIII-specific CAR-NKT cells for treating glioblastoma with enhanced efficacy and safety.","authors":"Yan-Ruide Li,Yichen Zhu,Zhe Li,Xinyuan Shen,Tyler Halladay,Christopher Tse,Yanxin Tian,Jie Huang,Annabel S Zhao,Nathan Y Ma,Catherine Zhang,David A Nathanson,Robert M Prins,Lili Yang","doi":"10.1016/j.ymthe.2025.09.026","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.09.026","url":null,"abstract":"Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor in adults, characterized by resistance to standard therapies including surgical resection, radiation, chemotherapy, and targeted agents. While chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has emerged as a promising immunotherapeutic approach for GBM, its application remains limited by tumor antigen escape, an immunosuppressive tumor microenvironment (TME), treatment-associated toxicities such as cytokine release syndrome (CRS), and the logistical complexities of autologous cell manufacturing. In this study, we leveraged hematopoietic stem and progenitor cell (HSPC) gene engineering combined with a feeder-free, ex vivo differentiation protocol to generate allogeneic EGFRvIII-specific CAR-engineered invariant natural killer T (AlloECAR-NKT) cells through a clinically guided, scalable platform. These cells exhibit potent, multifaceted antitumor activity against GBM, including direct tumor cell killing via CAR and NK receptors and selective targeting of CD1d+ immunosuppressive cells within the TME via their invariant TCR. In both subcutaneous and orthotopic GBM humanized models, AlloECAR-NKT cells demonstrated robust efficacy, minimal systemic leakage from the brain, and a reduced risk of CRS. Collectively, our findings support AlloECAR-NKT cells as a next-generation, off-the-shelf immunotherapy with enhanced efficacy and safety for the treatment of GBM.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"72 4 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056678","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}
引用次数: 0
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