Molecular Therapy最新文献_第8页

Emerging combined CAR-NK cell therapies in cancer treatment: Finding a dancing partner. 新出现的CAR-NK细胞联合疗法在癌症治疗中：寻找一个舞伴。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-01-03 DOI: 10.1016/j.ymthe.2024.12.057

Hamed Hosseinalizadeh, Li-Shu Wang, Hamed Mirzaei, Zohreh Amoozgar, Lei Tian, Jianhua Yu

{"title":"Emerging combined CAR-NK cell therapies in cancer treatment: Finding a dancing partner.","authors":"Hamed Hosseinalizadeh, Li-Shu Wang, Hamed Mirzaei, Zohreh Amoozgar, Lei Tian, Jianhua Yu","doi":"10.1016/j.ymthe.2024.12.057","DOIUrl":"10.1016/j.ymthe.2024.12.057","url":null,"abstract":"In recent decades, immunotherapy with chimeric antigen receptors (CARs) has revolutionized cancer treatment and given hope where other cancer therapies have failed. CAR-natural killer (NK) cells are NK cells that have been engineered ex vivo with a CAR on the cell membrane with high specificity for specific target antigens of tumor cells. The impressive results of several studies suggest that CAR-NK cell therapy has significant potential and successful performance in cancer treatment. Despite its effectiveness, CAR-NK cell therapy can have significant challenges when it comes to treating cancer. These challenges include tumor heterogeneity, antigen escape, an immunosuppressive tumor microenvironment, limited tissue migration from blood, exhaustion of CAR-NK cells, and inhibition by immunosuppressive checkpoint molecule signaling, etc. In CAR-T cell therapy, the use of combined approaches has shown encouraging outcomes for tumor regression and improved cancer treatment compared to single therapies. Therefore, to overcome these significant challenges in CAR-NK cells, innovative combination therapies of CAR-NK cells with other conventional therapies (e.g., chemotherapy and radiotherapy) or other immunotherapies are needed to counteract the above challenges and thereby increase the activity of CAR-NK cells. This review comprehensively discusses various cancer-treatment approaches in combination with CAR-NK cell therapy in the hope of providing valuable insights that may improve cancer treatment in the near future.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927662","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

ATGL regulates renal fibrosis by reprogramming lipid metabolism during the transition from AKI to CKD. ATGL通过重编程AKI向CKD过渡期间的脂质代谢调节肾纤维化。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-01-02 DOI: 10.1016/j.ymthe.2024.12.053

Xiaofan Li, Jianwen Chen, Jun Li, Yixuan Zhang, Jikai Xia, Hongjian Du, Chunjia Sheng, Mengjie Huang, Wanjun Shen, Guangyan Cai, Lingling Wu, Xueyuan Bai, Xiangmei Chen

{"title":"ATGL regulates renal fibrosis by reprogramming lipid metabolism during the transition from AKI to CKD.","authors":"Xiaofan Li, Jianwen Chen, Jun Li, Yixuan Zhang, Jikai Xia, Hongjian Du, Chunjia Sheng, Mengjie Huang, Wanjun Shen, Guangyan Cai, Lingling Wu, Xueyuan Bai, Xiangmei Chen","doi":"10.1016/j.ymthe.2024.12.053","DOIUrl":"10.1016/j.ymthe.2024.12.053","url":null,"abstract":"Acute kidney injury (AKI) can progress to chronic kidney disease (CKD) and subsequently to renal fibrosis. Poor repair of renal tubular epithelial cells (TECs) after injury is the main cause of renal fibrosis. Studies have shown that restoring damaged fatty acid β-oxidation (FAO) can reduce renal fibrosis. Adipose triglyceride lipase (ATGL) is a key enzyme that regulates lipid hydrolysis. This study, for the first time, demonstrated that ATGL was downregulated in the renal TEC in the AKI-CKD transition mouse model. Moreover, treatment with the ATGL inhibitor atglistatin exacerbated lipid accumulation and downregulated the FAO level and mitochondrial function, while it increased the level of oxidative stress injury and apoptosis, resulting in aggravated renal fibrosis. In contrast, ATGL overexpression suppressed lipid accumulation, improved the FAO level and mitochondrial function, and attenuated oxidative stress and apoptosis, thereby ameliorating fibrosis in vitro and in vivo. In summary, ATGL regulates renal fibrosis by reprogramming lipid metabolism in renal TECs. This study provided new avenues and targets for treating CKD.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922247","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

Hyperactive delta isoform of PI3 kinase enables long-distance regeneration of adult rat corticospinal tract. 过度活跃的PI3Kinase δ异构体使成年大鼠皮质脊髓束长距离再生。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-01-01 DOI: 10.1016/j.ymthe.2024.12.040

Kristyna Karova, Zuzana Polcanova, Lydia Knight, Stepanka Suchankova, Bart Nieuwenhuis, Radovan Holota, Vit Herynek, Lucia Machova Urdzikova, Rostislav Turecek, Jessica C Kwok, Joelle van den Herik, Joost Verhaagen, Richard Eva, James W Fawcett, Pavla Jendelova

{"title":"Hyperactive delta isoform of PI3 kinase enables long-distance regeneration of adult rat corticospinal tract.","authors":"Kristyna Karova, Zuzana Polcanova, Lydia Knight, Stepanka Suchankova, Bart Nieuwenhuis, Radovan Holota, Vit Herynek, Lucia Machova Urdzikova, Rostislav Turecek, Jessica C Kwok, Joelle van den Herik, Joost Verhaagen, Richard Eva, James W Fawcett, Pavla Jendelova","doi":"10.1016/j.ymthe.2024.12.040","DOIUrl":"10.1016/j.ymthe.2024.12.040","url":null,"abstract":"Neurons in the CNS lose regenerative potential with maturity, leading to minimal corticospinal tract (CST) axon regrowth after spinal cord injury (SCI). In young rodents, knockdown of PTEN, which antagonizes PI3K signaling by hydrolyzing PIP3, promotes axon regeneration following SCI. However, this effect diminishes in adults, potentially due to lower PI3K activation leading to reduced PIP3. This study explores whether increased PIP3 generation can promote long-distance regeneration in adults. We used a hyperactive PI3K, PI3Kδ (PIK3CD), to boost PIP3 levels in mature cortical neurons and assessed CST regeneration after SCI. Adult rats received AAV1-PIK3CD and AAV1-eGFP, or AAV1-eGFP alone, in the sensorimotor cortex concurrent with a C4 dorsal SCI. Transduced neurons showed increased pS6 levels, indicating elevated PI3K/Akt/mTOR signaling. CST regeneration, confirmed with retrograde tracing, was evaluated up to 16 weeks post injury. At 12 weeks, ∼100 axons were present at lesion sites, doubling to 200 by 16 weeks, with regeneration indices of 0.1 and 0.2, respectively. Behavioral tests showed significant improvements in paw reaching, grip strength, and ladder-rung walking in PIK3CD-treated rats, corroborated by electrophysiological recordings of cord dorsum potentials and distal flexor muscle electromyography. Thus, PI3Kδ upregulation in adult cortical neurons enhances axonal regeneration and functional recovery post SCI.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922249","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

KCNN4 as a genomic determinant of cytosolic delivery by the attenuated cationic lytic peptide L17E. KCNN4作为减毒阳离子裂解肽L17E细胞质递送的基因组决定因素。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2025-01-01 DOI: 10.1016/j.ymthe.2024.12.050

Masashi Kuriyama, Hisaaki Hirose, Yoshimasa Kawaguchi, Junya Michibata, Masashi Maekawa, Shiroh Futaki

{"title":"KCNN4 as a genomic determinant of cytosolic delivery by the attenuated cationic lytic peptide L17E.","authors":"Masashi Kuriyama, Hisaaki Hirose, Yoshimasa Kawaguchi, Junya Michibata, Masashi Maekawa, Shiroh Futaki","doi":"10.1016/j.ymthe.2024.12.050","DOIUrl":"10.1016/j.ymthe.2024.12.050","url":null,"abstract":"The development of a cytosolic delivery strategy for biopharmaceuticals is one of the central issues in drug development. Knowledge of the mechanisms underlying these processes may also pave the way for the discovery of novel delivery systems. L17E is an attenuated cationic amphiphilic lytic (ACAL) peptide developed by our research group that shows promise for cytosolic antibody delivery. In this study, given the high efficacy of L17E in cytosolic delivery, we investigated the mechanism of action of L17E in detail. L17E was found to achieve cytosolic delivery predominantly by transient disruption of the plasma membrane without the need for endocytosis. Importantly, the cell-line selectivity studies of L17E revealed a strong correlation between the efficiency of L17E-mediated delivery and the expression level of KCNN4, the gene encoding the calcium-activated potassium channel KCa3.1. Genetic and pharmacological regulation of KCNN4 expression and KCa3.1 activity, respectively, correlate closely with the efficiency of L17E-mediated cytosolic delivery, suggesting the importance of membrane-potential regulation by extracellular Ca2+ influx. Therefore, the activity of the L17E is relevant to the calcium-activated potassium channel.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922250","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

Controlling intracellular protein delivery, tumor colonization and tissue distribution using the master regulator flhDC in a clinically relevant ΔsseJ Salmonella strain. 在临床相关ΔsseJ沙门氏菌菌株中使用主调节剂flhDC控制细胞内蛋白递送，肿瘤定植和组织分布。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-31 DOI: 10.1016/j.ymthe.2024.12.038

Vishnu Raman, Christopher L Hall, Victoria E Wetherby, Samantha A Witney, Nele Van Dessel, Neil S Forbes

{"title":"Controlling intracellular protein delivery, tumor colonization and tissue distribution using the master regulator flhDC in a clinically relevant ΔsseJ Salmonella strain.","authors":"Vishnu Raman, Christopher L Hall, Victoria E Wetherby, Samantha A Witney, Nele Van Dessel, Neil S Forbes","doi":"10.1016/j.ymthe.2024.12.038","DOIUrl":"https://doi.org/10.1016/j.ymthe.2024.12.038","url":null,"abstract":"Effectively targeting intracellular pathways in cancers requires a system that specifically delivers to tumors and internalizes into cancer cells. To achieve this goal, we developed intracellular-delivering (ID) Salmonella with controllable expression of flhDC, to regulate flagella production and cell invasion. We hypothesized that controlling flhDC would overcome the poor colonization seen in prior clinical trials. To test this hypothesis, we incorporated the aspirin-responsive Psal promoter and tuned flhDC expression with ssra degradation tags. In tumor-bearing mice, controlling flhDC increased protein release, tissue dispersion and tumor colonization more than ten million times. We discovered that inducing flhDC increases escape from intracellular vacuoles; however, deleting sseJ prevented escape and further increased protein delivery. Delivering constitutively active caspase-3 with ID-f-s Salmonella (ΔsseJ and induced PSal-flhDC) induced cell death in pancreatic, breast and liver cancer cells and reduced the growth of breast tumors. This clinically ready strain preferentially colonized metastatic breast tissue 280 and 800 times more than surrounding healthy tissue in the lung and liver, respectively. By precisely controlling tumor colonization and cell invasion, this strain overcomes critical limitations of bacterial therapy and will enable treatment of many hard-to-treat cancers444.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915308","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 nucleoside-modified rabies mRNA vaccine induces long-lasting and comprehensive immune responses in mice and non-human primates. 核苷修饰的狂犬病mRNA疫苗在小鼠和非人灵长类动物中诱导持久和全面的免疫应答。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-31 DOI: 10.1016/j.ymthe.2024.12.041

Yu Wang, Shen Wang, Lulu Huang, Wenhao Mao, Fangmeng Li, Ang Lin, Weijun Zhao, Xianhuan Zeng, Yue Zhang, Dingcao Yang, Yuhong Han, Yidan Li, Leyuan Ren, Ying Li, Liang Zhang, Feihu Yan, Yong Yang, Xinying Tang

{"title":"A nucleoside-modified rabies mRNA vaccine induces long-lasting and comprehensive immune responses in mice and non-human primates.","authors":"Yu Wang, Shen Wang, Lulu Huang, Wenhao Mao, Fangmeng Li, Ang Lin, Weijun Zhao, Xianhuan Zeng, Yue Zhang, Dingcao Yang, Yuhong Han, Yidan Li, Leyuan Ren, Ying Li, Liang Zhang, Feihu Yan, Yong Yang, Xinying Tang","doi":"10.1016/j.ymthe.2024.12.041","DOIUrl":"10.1016/j.ymthe.2024.12.041","url":null,"abstract":"Rabies is a lethal zoonotic infectious disease. Vaccines against the rabies virus have significantly reduced the number of deaths from the disease. However, all licensed rabies vaccines are inactivated vaccines, which have limited immunogenicity and complicated immunization procedures. A novel vaccine that provides sustained and comprehensive protection is urgently needed. Here, we developed a novel rabies mRNA vaccine candidate containing sequence-optimized mRNAs encoding full-length glycoprotein encapsulated in ionizable lipid nanoparticles. In mice and rhesus macaques, the rabies mRNA exhibited superior immunogenicity over licensed vaccines, especially in inducing long-lasting neutralizing antibodies and memory B cells. A single administration of 1.5 μg mRNA vaccine could provide complete protection against a lethal rabies virus challenge in mice. Additionally, the mRNA vaccine could robustly activate cellular immune responses with moderate release of several cytokines. In summary, our data demonstrated that the rabies mRNA vaccine outperformed approved inactivated vaccines in both mice and rhesus macaques. This highlights the potential of the mRNA platform in developing next-generation rabies vaccines.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915303","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

Autologous transplantation of mitochondria/rAAV IGF-I platforms in human osteoarthritic articular chondrocytes as a novel therapeutic concept for human osteoarthritis. 线粒体/rAAV IGF-I平台在人骨关节炎关节软骨细胞内的自体移植作为治疗人骨关节炎的新概念

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-30 DOI: 10.1016/j.ymthe.2024.12.047

Gang Zhong, Wei Liu, Jagadeesh K Venkatesan, Dan Wang, Henning Madry, Magali Cucchiarini

{"title":"Autologous transplantation of mitochondria/rAAV IGF-I platforms in human osteoarthritic articular chondrocytes as a novel therapeutic concept for human osteoarthritis.","authors":"Gang Zhong, Wei Liu, Jagadeesh K Venkatesan, Dan Wang, Henning Madry, Magali Cucchiarini","doi":"10.1016/j.ymthe.2024.12.047","DOIUrl":"https://doi.org/10.1016/j.ymthe.2024.12.047","url":null,"abstract":"Despite various available treatments, highly prevalent osteoarthritis cannot be cured in patients. In light of evidence showing mitochondria dysfunction during the disease progression, our goal was to develop a novel therapeutic concept based on the transplantation of mitochondria as platforms to deliver recombinant adeno-associated viral (rAAV) gene vectors with a potency for osteoarthritis. For the first time to our best knowledge, we report the successful creation of a safe mitochondria/rAAV system effectively promoting the overexpression of a candidate insulin-like growth factor I (IGF-I) by administration to autologous human osteoarthritic articular chondrocytes versus control conditions (reporter mitochondria/rAAV lacZ system, rAAV-free system, absence of mitochondria transplantation) (up to 8.4-fold difference). The candidate mitochondria/rAAV IGF-I system significantly improved key activities in the transplanted cells (proliferation/survival, extracellular matrix production, mitochondria functions) relative to the control conditions (up to 9.5-fold difference), including when provided in a PF127 hydrogel for reinforced delivery (up to 5.9-fold difference). Such effects were accompanied with increased levels of cartilage-specific SOX9 and Mfn-1 (mitochondria fusion) and with decreased levels of Drp-1 (mitochondria fission) and proinflammatory TNF-α (up to 4.5-fold difference). This study shows the potential of combining the use of mitochondria with rAAV as a promising approach for human OA.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915307","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

Impaired megakaryopoiesis due to aberrant macrophage polarization via BTK/Rap1/NF-κB pathway in sepsis-induced thrombocytopenia. 脓毒症所致血小板减少症中巨噬细胞异常极化通过BTK/Rap1/NF-κB通路导致巨核生成受损

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-30 DOI: 10.1016/j.ymthe.2024.12.048

Ziyan Zhang, Meng Zhou, Yaqiong Tang, Jiaqian Qi, Xiaoyan Xu, Peng Wang, Haohao Han, Tingting Pan, Xiaofei Song, Shuhui Jiang, Xueqian Li, Chengyuan Gu, Zhenzhen Yao, Qixiu Hou, Mengting Guo, Siyi Lu, Depei Wu, Yue Han

{"title":"Impaired megakaryopoiesis due to aberrant macrophage polarization via BTK/Rap1/NF-κB pathway in sepsis-induced thrombocytopenia.","authors":"Ziyan Zhang, Meng Zhou, Yaqiong Tang, Jiaqian Qi, Xiaoyan Xu, Peng Wang, Haohao Han, Tingting Pan, Xiaofei Song, Shuhui Jiang, Xueqian Li, Chengyuan Gu, Zhenzhen Yao, Qixiu Hou, Mengting Guo, Siyi Lu, Depei Wu, Yue Han","doi":"10.1016/j.ymthe.2024.12.048","DOIUrl":"10.1016/j.ymthe.2024.12.048","url":null,"abstract":"Sepsis-induced thrombocytopenia (SIT) is a widely accepted predictor of poor prognosis during sepsis, while the mechanism of SIT remains elusive. In this study, we revealed that SIT patients and septic mice exhibited higher levels of pro-inflammatory macrophages and phosphorylated Bruton's tyrosine kinase (p-BTK) expression in macrophages, which were closely correlated with platelet counts. Treatment with the BTK inhibitor BGB-3111 in SIT mice resulted in enhanced production of megakaryocytes and platelets. Depletion of macrophages in SIT mice and coculture experiments further confirmed the critical role of macrophages in the improvement of platelet count induced by BGB-3111. By performing single-cell RNA sequencing on bone marrow-derived cells from SIT mice, we not only confirmed the connection between macrophages and megakaryocytes influenced by BTK but also identified a potential mediation through the Rap1 signaling pathway in macrophages. Subsequent experiments in macrophages demonstrated that inhibition of BTK signaling impeded the pro-inflammatory polarization of macrophages by targeting the Rap1/NF-κB signaling pathway. In conclusion, our study highlights the crucial role of macrophages in SIT, and inhibiting phosphorylation of BTK in macrophages may alleviate SIT through the Rap1/NF-κB signaling pathway.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915312","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

Recent developments in translational imaging of in vivo gene therapy outcomes. 体内基因治疗结果转化成像的最新进展。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-30 DOI: 10.1016/j.ymthe.2024.12.049

Isabel L Day, Mikayla Tamboline, Gerald S Lipshutz, Shili Xu

{"title":"Recent developments in translational imaging of in vivo gene therapy outcomes.","authors":"Isabel L Day, Mikayla Tamboline, Gerald S Lipshutz, Shili Xu","doi":"10.1016/j.ymthe.2024.12.049","DOIUrl":"10.1016/j.ymthe.2024.12.049","url":null,"abstract":"Gene therapy achieves therapeutic benefits by delivering genetic materials, packaged within a delivery vehicle, to target cells with defective genes. This approach has shown promise in treating various conditions, including cancer, metabolic disorders, and tissue-degenerative diseases. Over the past 5 years, molecular imaging has increasingly supported gene therapy development in both preclinical and clinical studies. High-quality images from positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and computed tomography (CT) enable quantitative and reliable monitoring of gene therapy. Most reported studies have applied imaging biomarkers to non-invasively evaluate the outcomes of gene therapy. This review aims to inform researchers in molecular imaging and gene therapy about the integration of these two disciplines. We highlight recent developments in using imaging biomarkers to monitor the outcome of in vivo gene therapy, where the therapeutic delivery vehicle is administered systemically. In addition, we discuss prospects for further incorporating imaging biomarkers to support the development and application of gene therapy.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915323","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

Understanding the interplay between oHSV and the host immune system: Implications for therapeutic oncolytic virus development. 了解oHSV与宿主免疫系统之间的相互作用：对溶瘤病毒治疗发展的影响。

IF 12.1 1区医学

Molecular Therapy Pub Date : 2024-12-30 DOI: 10.1016/j.ymthe.2024.12.054

Kalkidan Ayele, Hiroaki Wakimoto, Hans J Nauwynck, Howard L Kaufman, Samuel D Rabkin, Dipongkor Saha

{"title":"Understanding the interplay between oHSV and the host immune system: Implications for therapeutic oncolytic virus development.","authors":"Kalkidan Ayele, Hiroaki Wakimoto, Hans J Nauwynck, Howard L Kaufman, Samuel D Rabkin, Dipongkor Saha","doi":"10.1016/j.ymthe.2024.12.054","DOIUrl":"10.1016/j.ymthe.2024.12.054","url":null,"abstract":"Oncolytic herpes simplex viruses (oHSV) preferentially replicate in cancer cells while inducing antitumor immunity, and thus, they are often referred to as in situ cancer vaccines. OHSV infection of tumors elicits diverse host immune responses comprising both innate and adaptive components. Although the innate and adaptive immune responses primarily target the tumor, they also contribute to antiviral immunity, limiting viral replication/oncolysis. OHSV-encoded proteins use various mechanisms to evade host antiviral pathways and immune recognition, favoring oHSV replication, oncolysis, and spread. In general, oHSV infection and replication within tumors results in a series of sequential events, such as oncolysis and release of tumor and viral antigens, dendritic cell-mediated antigen presentation, T cell priming and activation, T cell trafficking and infiltration to tumors, and T cell recognition of cancer cells, leading to tumor (and viral) clearance. These sequential events align with all steps of the cancer-immunity cycle. However, a comprehensive understanding of the interplay between oHSV and host immune responses is crucial to optimize oHSV-induced antitumor immunity and efficacy. Therefore, this review aims to elucidate oHSV's communication with innate and adaptive immune systems and use such interactions to improve oHSV's potential as a potent immunovirotherapeutic agent against cancer.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915331","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