Molecular Therapy最新文献

Modulation of the unfolded protein response with a C-terminal fragment of MANF facilitates recovery in models of multiple sclerosis. 用MANF的c端片段调节未折叠蛋白反应有助于多发性硬化症模型的恢复。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-10-11 DOI: 10.1016/j.ymthe.2025.10.023

Tapani K Koppinen,Carolina R Reyes,Jinhan Nam,Aastha Singh,Shibajee Mandal,Liam Beckett,Alba Montedeoca,Tuomas A E Kallionpää,Maria Lindahl,Francisco J Rivera,Merja H Voutilainen

{"title":"Modulation of the unfolded protein response with a C-terminal fragment of MANF facilitates recovery in models of multiple sclerosis.","authors":"Tapani K Koppinen,Carolina R Reyes,Jinhan Nam,Aastha Singh,Shibajee Mandal,Liam Beckett,Alba Montedeoca,Tuomas A E Kallionpää,Maria Lindahl,Francisco J Rivera,Merja H Voutilainen","doi":"10.1016/j.ymthe.2025.10.023","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.10.023","url":null,"abstract":"Inflammation in multiple sclerosis leads to chronic activation of a cellular stress mechanism, the unfolded protein response (UPR), which is thought to both exacerbate neuroinflammation and prevent regenerative tissue responses such as remyelination. The UPR-modulating protein MANF has shown great promise for attenuating chronic UPR activation and enhancing tissue regeneration in various disease models but does not reach the CNS when given peripherally. We utilized C-MANF, a C-terminal fragment of MANF, and showed that subcutaneous administration of C-MANF promoted motor function recovery and tissue regeneration in a mouse model of autoimmune demyelination. We demonstrated that C-MANF suppresses neuroinflammatory activation and facilitates the recovery of oligodendrocytes after demyelination, while reducing long-term activation of the UPR. Furthermore, we showed that C-MANF enhances myelination of primary OPCs in culture, that promotion of remyelination in cerebellar organotypic slice cultures is dependent on UPR-modulation, and that exogenously applied C-MANF suppresses chronic activation of all three UPR pathways in oligodendroglia. Finally, we showed that demyelination in MANF-deficient brains leads to extensive neuroinflammation and CNS degeneration, implicating UPR-modulation by MANF as a key component in tissue responses to demyelination. Altogether, we show that UPR modulation with C-MANF is a promising new therapeutic approach for treating neuroinflammatory demyelination.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"209 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277209","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

Pancreatic Transdifferentiation of NOD Mouse Livers Prevented Development of Hyperglycemia. NOD小鼠肝脏胰腺转分化可防止高血糖的发生。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-10-11 DOI: 10.1016/j.ymthe.2025.10.021

Alexandra L G Mahoney,Binhai Ren,Najah T Nassif,Bronwyn A O'Brien,Grant J Logan,Catherine A Gorrie,Ian E Alexander,Ann M Simpson

{"title":"Pancreatic Transdifferentiation of NOD Mouse Livers Prevented Development of Hyperglycemia.","authors":"Alexandra L G Mahoney,Binhai Ren,Najah T Nassif,Bronwyn A O'Brien,Grant J Logan,Catherine A Gorrie,Ian E Alexander,Ann M Simpson","doi":"10.1016/j.ymthe.2025.10.021","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.10.021","url":null,"abstract":"Type 1 diabetes (T1D) is caused by the autoimmune destruction of the pancreatic insulin producing beta (β)-cells. This study investigated a novel gene therapy approach to prevent disease development by replacing pancreatic β-cell function with that from transdifferentiated liver cells. A clinically applicable third-generation lentiviral vector was used to deliver a cocktail of β-cell transcription factors (Pdx1, ND1 and MafA) to the portal vein of 5-6-week-old non-obese diabetic (NOD) mice. At the experimental endpoint (30-weeks), 100% of the NOD mice that received the lentiviral vector expressing the three β-cell transcription factors were normoglycemic. Additionally, intraperitoneal glucose tolerance tests revealed that treated NOD mice could normalise blood glucose concentrations as efficiently as non-diabetic control animals. RT-PCR detected a range of pancreatic markers, such as somatostatin, Glut 2 and most importantly mouse insulin (INS1 and INS2), which was also found to be stored in the liver. Liver function tests remained normal. Collectively, this data shows expression of these β-cell transcription factors led to partial pancreatic transdifferentiation and halted the development of hyperglycemia and abnormal glucose tolerance, which are the hallmarks of T1D. Thus, this approach holds substantial promise as a potential prophylactic strategy.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"20 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277208","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

Extracellular Vesicles-Associated AAVs for the treatment of Machado-Joseph Disease. 细胞外小泡相关aav治疗Machado-Joseph病。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-10-11 DOI: 10.1016/j.ymthe.2025.10.022

Carina Henriques,Patrícia Albuquerque,David Rufino-Ramos,Miguel M Lopes,Kevin Leandro,Catarina Miranda,Rita Almeida,Guilherme Gabriel,João de Sousa-Lourenço,Sara M Lopes,Laetitia S Gaspar,Diana Lobo,Ana Carolina Silva,Teresa M Ribeiro-Rodrigues,Henrique Girão,Célia M Gomes,Rafael Baganha,Sónia Duarte,Casey A Maguire,Magda M Santana,Luís Pereira de Almeida,Rui Jorge Nobre

{"title":"Extracellular Vesicles-Associated AAVs for the treatment of Machado-Joseph Disease.","authors":"Carina Henriques,Patrícia Albuquerque,David Rufino-Ramos,Miguel M Lopes,Kevin Leandro,Catarina Miranda,Rita Almeida,Guilherme Gabriel,João de Sousa-Lourenço,Sara M Lopes,Laetitia S Gaspar,Diana Lobo,Ana Carolina Silva,Teresa M Ribeiro-Rodrigues,Henrique Girão,Célia M Gomes,Rafael Baganha,Sónia Duarte,Casey A Maguire,Magda M Santana,Luís Pereira de Almeida,Rui Jorge Nobre","doi":"10.1016/j.ymthe.2025.10.022","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.10.022","url":null,"abstract":"Machado-Joseph disease (MJD) is the most common dominant autosomal inherited ataxia worldwide, caused by the over-repetition of the trinucleotide CAG in the ATXN3 gene. This leads to the accumulation of ataxin-3 protein and neurodegeneration. Currently, treatment remains symptomatic, though gene therapy has emerged as a promising approach. However, efficient and minimally invasive delivery to the brain remains a challenge. Extracellular vesicle-associated adeno-associated vectors (EV-AAVs) are a novel delivery system, combining AAVs' ability to deliver genes with extracellular vesicles' capacity to bypass the immune system and cross the blood-brain barrier (BBB). Previous studies, however, have only combined AAV serotypes known to efficiently cross the BBB with EVs as a non-invasive delivery system to the brain. Thus, the ability of EV-AAVs to cross the BBB remained inconclusive. In this study we evaluated whether AAV1/2 serotype, combined with rabies virus glycoprotein (RVg)-coated EVs, could effectively target the brain. Two isolation methods, differential ultracentrifugation and size exclusion chromatography (SEC) were compared, with SEC yielding higher EV recovery. Moreover, RVg-EV-AAV1/2 successfully crossed the BBB and transduced mouse brains, leading to motor and neuropathological improvements in an MJD mouse model. This study demonstrates that RVg-EV-AAVs are promising non-invasive delivery systems for MJD gene therapy.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"159 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277207","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

A rapid immunization and antibody redesign platform for discovering broadly neutralizing antibodies against non-immunized SARS-CoV-2 variant. 一个快速免疫和抗体重新设计平台，用于发现针对非免疫SARS-CoV-2变体的广泛中和抗体。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-10-11 DOI: 10.1016/j.ymthe.2025.10.020

Shusei Hamamichi,Narumi Uno,Kazuto Shimoya,Takato Fukushima,Marina Abe,Arata Watanabe,Mizuho Ito,Yuko Wakasa,Yuko Yajima,Rio Suzuki,Natsumi Miyazaki,Akifumi Kamiyama,Kana Uno,Masaharu Hiratsuka,Takashi Moriwaki,Tomokazu Tamura,Kyosuke Kanai,Satoshi Abe,Takasuke Fukuhara,Seiji Kageyama,Masayuki Su'etsugu,Yasuhiro Kazuki,Kazuma Tomizuka

{"title":"A rapid immunization and antibody redesign platform for discovering broadly neutralizing antibodies against non-immunized SARS-CoV-2 variant.","authors":"Shusei Hamamichi,Narumi Uno,Kazuto Shimoya,Takato Fukushima,Marina Abe,Arata Watanabe,Mizuho Ito,Yuko Wakasa,Yuko Yajima,Rio Suzuki,Natsumi Miyazaki,Akifumi Kamiyama,Kana Uno,Masaharu Hiratsuka,Takashi Moriwaki,Tomokazu Tamura,Kyosuke Kanai,Satoshi Abe,Takasuke Fukuhara,Seiji Kageyama,Masayuki Su'etsugu,Yasuhiro Kazuki,Kazuma Tomizuka","doi":"10.1016/j.ymthe.2025.10.020","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.10.020","url":null,"abstract":"From the COVID-19, we learned valuable lessons related to development of broadly neutralizing antibodies (bnAbs). Here, we present a discovery platform termed Express Hu-mAb System that integrated fully human Ab-producing trans-chromosomic (TC-mAb) mouse, rapid immunization procedure, and CHO cell-based mammalian display system (MDS) to generate bnAbs against the non-immunized SARS-CoV-2 variant in 60-90 days. Rapid 30-day immunization of TC-mAb mouse resulted in increased titers, elevated antibody concentration, and production of anti-serum that neutralized the non-immunized BA.1. Single B cell analysis without using fluorescent antigen probe identified clonotypes that recapitulated immune responses associated with the COVID-19. Importantly, we generated 25 bnAb candidates based on the abundance of sequence reads, determined 14 binders (56%), and identified clonotype 11 as a bnAb that neutralized the non-immunized BA.5 in 60 days. Next, exploiting a TC-mAb mouse whose anti-serum neutralized only the Wuhan strain, we constructed a chain-shuffled immunoglobulin cDNA library with sufficient diversity of 4.3-6.2 x 104 CHO cells. We then applied the MDS to redesign bnAb candidates, and identified M5419S09Ab01 that neutralized the BA.5 in 90 days. Taken together, this work demonstrates speed, efficiency, and simplicity of our platform to discover bnAbs against the phylogenetically distinct viral variant with optimal developability and manufacturability.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"119 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277289","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

CRISPR for cystic fibrosis: Advances and insights from a systematic review. CRISPR治疗囊性纤维化：系统综述的进展和见解

IF 12 1区医学

Molecular Therapy Pub Date : 2025-10-08 DOI: 10.1016/j.ymthe.2025.09.046

Lucia Nicosia, Patrick T Harrison

引用次数: 0

Cancer Viroimmunotherapy Platforms Based on Varicella-Zoster Virus and Cytomegalovirus. 基于水痘带状疱疹病毒和巨细胞病毒的癌症病毒免疫治疗平台。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-10-06 DOI: 10.1016/j.ymthe.2025.10.004

Haifei Jiang,Kah Whye Peng,Stephen J Russell

引用次数: 0

Podocyte-directed VEGFC gene therapy prevents increased glomerular permeability and glycocalyx damage in a mouse model of type 1 diabetes. 足细胞导向的VEGFC基因治疗可防止1型糖尿病小鼠模型肾小球通透性增加和糖萼损伤。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-10-06 DOI: 10.1016/j.ymthe.2025.10.001

Aldara Martin Alonso,Carl May,Holly Stowell-Connolly,Haijie Wu,Monica Gamez,Khadija Ourradi,Raina Ramnath,Wen Ding,Gavin I Welsh,Simon C Satchell,Rebecca R Foster

{"title":"Podocyte-directed VEGFC gene therapy prevents increased glomerular permeability and glycocalyx damage in a mouse model of type 1 diabetes.","authors":"Aldara Martin Alonso,Carl May,Holly Stowell-Connolly,Haijie Wu,Monica Gamez,Khadija Ourradi,Raina Ramnath,Wen Ding,Gavin I Welsh,Simon C Satchell,Rebecca R Foster","doi":"10.1016/j.ymthe.2025.10.001","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.10.001","url":null,"abstract":"Diabetic kidney disease (DKD) is the leading cause of end-stage renal failure, and current interventions fail to directly target the glomerulus, where the disease initiates. Vascular endothelial growth factor (VEGF)C is a key contributor to glomerular endothelial barrier function. In transgenic mice, podocyte-specific overexpression of human VEGFC was protective in early DKD. Here, we investigated the therapeutic potential of a podocyte-targeted VEGFC gene therapy in DKD. We employed an adeno-associated virus vector (AAV2/9) to drive human VEGFC in human and mouse podocytes. Expressed VEGFC was functional in vitro. In type 1 diabetic mice (induced by streptozotocin), systemic administration of AAV2/9 increased glomerular human VEGFC expression, ameliorating albuminuria and increased glomerular permeability. Importantly, VEGFC gene therapy also protected the glomerular endothelial glycocalyx, the first barrier to protein in the glomerular filtration barrier. These findings demonstrate that podocyte-directed VEGFC gene delivery can restore glomerular function and protect against early DKD progression. This novel approach represents a promising therapeutic strategy, particularly for patients with type 1 diabetes at risk of DKD, where there is an unmet clinical need.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"30 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240928","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

Comparative analysis of RNA versus protein splicing in dual AAV-mediated gene therapy in a mouse model of DFNB9 deafness. 双aav介导的基因治疗小鼠DFNB9耳聋模型中RNA与蛋白剪接的比较分析。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-10-06 DOI: 10.1016/j.ymthe.2025.10.002

Mengzhao Xun,Xintai Fan,Hui Wang,Jingjing Zhao,Gongrui Tang,Weida Zhang,Shaowei Hu,Longlong Zhang,Daqi Wang,Yuxin Chen,Jianping Liu,Honghai Tang,Geng-Lin Li,Bing Chen,Yilai Shu

{"title":"Comparative analysis of RNA versus protein splicing in dual AAV-mediated gene therapy in a mouse model of DFNB9 deafness.","authors":"Mengzhao Xun,Xintai Fan,Hui Wang,Jingjing Zhao,Gongrui Tang,Weida Zhang,Shaowei Hu,Longlong Zhang,Daqi Wang,Yuxin Chen,Jianping Liu,Honghai Tang,Geng-Lin Li,Bing Chen,Yilai Shu","doi":"10.1016/j.ymthe.2025.10.002","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.10.002","url":null,"abstract":"Pathological mutations in the OTOF gene cause autosomal recessive deafness 9 (DFNB9). Although dual-AAV gene replacement therapy has been shown to partially rescue the hearing of patients with DFNB9, the therapeutic effects still need further exploration. To investigate the impact of different recombination strategies on the efficacy of OTOF gene therapy, we constructed five dual-AAV1 therapeutic agents using RNA or protein splicing principles. Based on the recombination strategy using RNA splicing, the AAV1-AK system rescued the hearing of Otof-/- mice to 55-70 dB, which outperformed the AAV1-AP and AAV1-TS systems. Based on protein splicing, the AAV1-intein system rescued the hearing of Otof-/- mice to 35-70 dB, which outperformed that of AAV1-AK, and the effects lasted up to 12 months after injection in both newborn and adult mice. The efficacy of otoferlin re-expression and the number and functional restoration of ribbon synapses in the AAV1-intein system were also better than the AAV1-AK system. These results show that protein recombination is more efficient than nucleic acid recombination for gene therapy in DFNB9. Therefore, this work not only provides data for optimization of DFNB9 gene therapy, but also provides a reference for the delivery of other large genes.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"80 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240926","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

Gene supplementation with precise transgene expression rescues hearing loss in a mouse model with an Mpzl2 East Asian founder variant. 在Mpzl2东亚始祖变异体小鼠模型中，精确转基因表达的基因补充可挽救听力损失。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-10-06 DOI: 10.1016/j.ymthe.2025.10.005

Seung Hyun Jang,Hyeong Gi Song,Sun Young Joo,Jung Ah Kim,Se Jin Kim,Jae Young Choi,Jinsei Jung,Heon Yung Gee

{"title":"Gene supplementation with precise transgene expression rescues hearing loss in a mouse model with an Mpzl2 East Asian founder variant.","authors":"Seung Hyun Jang,Hyeong Gi Song,Sun Young Joo,Jung Ah Kim,Se Jin Kim,Jae Young Choi,Jinsei Jung,Heon Yung Gee","doi":"10.1016/j.ymthe.2025.10.005","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.10.005","url":null,"abstract":"Hearing loss is the most common sensory organ disorder, with genetic factors substantially contributing to the disease. Among the 87 genes responsible for autosomal recessive nonsyndromic hearing loss, mutations in MPZL2 have been frequently linked to mild-to-moderate autosomal recessive hearing loss (DFNB111). Here, we present multiple families whose hearing loss arose from biallelic mutations in the MPZL2 gene and found that the MPZL2 p.Q74* mutation may be a founder allele among East Asians. Furthermore, we generated an Mpzl2 p.Q74* knock-in mouse model that exhibited autosomal recessive, progressive, ski-sloping hearing loss with Deiter's cell degeneration. Gene supplementation using AAV-DJ or AAV-PHP.eB to deliver human MPZL2 (hMPZL2) under control of the CAG promoter induced ototoxicity, whereas employing an alternative EF1α promoter with AAV-DJ (DJ-EF1α-hMPZL2) circumvented this issue, restoring long-term auditory function and Deiter's cell survival in Mpzl2Q74∗/Q74∗ mice for up to 24 weeks. Overall, this study provides the foundational steps for developing a safe and effective biological treatment for DFNB111 and underscores the importance of precise regulation of target cells and transgene expression in AAV-based treatments.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"56 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240930","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

Innate Immune Cells in Chimeric Antigen Receptor Therapy. 嵌合抗原受体治疗中的先天免疫细胞。

IF 12.4 1区医学

Molecular Therapy Pub Date : 2025-10-06 DOI: 10.1016/j.ymthe.2025.10.003

Marius Jassaud,Lydia Ziane-Chaouche,Marie Duhamel,Michel Salzet

{"title":"Innate Immune Cells in Chimeric Antigen Receptor Therapy.","authors":"Marius Jassaud,Lydia Ziane-Chaouche,Marie Duhamel,Michel Salzet","doi":"10.1016/j.ymthe.2025.10.003","DOIUrl":"https://doi.org/10.1016/j.ymthe.2025.10.003","url":null,"abstract":"Chimeric antigen receptor (CAR) therapies have revolutionized cancer treatment, particularly with the success of CAR-T cells in hematologic malignancies. However, their application to solid tumors remains limited by major challenges, including cytokine release syndrome (CRS), neurotoxicity, poor tumor infiltration, antigen heterogeneity, and high manufacturing costs. These limitations have prompted growing interest in alternative immune effector cells. Innate immune cells - such as natural killer (NK) cells, macrophages, invariant natural killer T (iNKT) cells, gamma delta (γδ) T cells, dendritic cells (DCs) and neutrophils - offer distinct advantages. They are associated with a lower risk of graft-versus-host disease (GvHD), possess intrinsic tumor-homing and cytotoxic properties, and are suitable for off-the-shelf therapeutic platforms. This review explores the biological rationale and clinical potential of CAR-engineered innate immune cells, highlighting key findings from preclinical and clinical studies. Finally, we discuss combinatorial strategies and future directions that could shape the next generation of CAR-based therapies for solid tumors.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"19 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240932","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