Pub Date : 2024-08-01Epub Date: 2024-06-11DOI: 10.1016/j.molmed.2024.05.018
Quazi T H Shubhra, Tivadar Feczkó, Qiang Cai
Mendez-Gomez et al. recently demonstrated the transformative potential of RNA-lipid particle aggregates (RNA-LPAs) in immunotherapy. By reprogramming the tumor microenvironment (TME) and potentiating antitumor immunity, RNA-LPAs target primary tumors and elicit robust systemic immunity. This innovative platform holds promise for translating preclinical success into tangible clinical benefits.
{"title":"Beyond the danger signal: RNA aggregates orchestrate immunotherapy.","authors":"Quazi T H Shubhra, Tivadar Feczkó, Qiang Cai","doi":"10.1016/j.molmed.2024.05.018","DOIUrl":"10.1016/j.molmed.2024.05.018","url":null,"abstract":"<p><p>Mendez-Gomez et al. recently demonstrated the transformative potential of RNA-lipid particle aggregates (RNA-LPAs) in immunotherapy. By reprogramming the tumor microenvironment (TME) and potentiating antitumor immunity, RNA-LPAs target primary tumors and elicit robust systemic immunity. This innovative platform holds promise for translating preclinical success into tangible clinical benefits.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311823","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 : 2024-08-01Epub Date: 2024-06-17DOI: 10.1016/j.molmed.2024.05.014
Alberto L Epstein, Samuel D Rabkin
Herpes simplex virus type 1 (HSV-1) is a DNA virus and human pathogen used to construct promising therapeutic vectors. HSV-1 vectors fall into two classes: replication-selective oncolytic vectors for cancer therapy and defective non-replicative vectors for gene therapy. Vectors from each class can accommodate ≥30 kb of inserts, have been approved clinically, and demonstrate a relatively benign safety profile. Despite oncolytic HSV (oHSV) replication in tumors and elicited immune responses, the virus is well tolerated in cancer patients. Current non-replicative vectors elicit only limited immune responses. Seropositivity and immune responses against HSV-1 do not eliminate either the vector or infected cells, and the vectors can therefore be re-administered. In this review we highlight vectors that have been translated to the clinic and host-virus immune interactions that impact on the safety and efficacy of HSVs.
{"title":"Safety of non-replicative and oncolytic replication-selective HSV vectors.","authors":"Alberto L Epstein, Samuel D Rabkin","doi":"10.1016/j.molmed.2024.05.014","DOIUrl":"10.1016/j.molmed.2024.05.014","url":null,"abstract":"<p><p>Herpes simplex virus type 1 (HSV-1) is a DNA virus and human pathogen used to construct promising therapeutic vectors. HSV-1 vectors fall into two classes: replication-selective oncolytic vectors for cancer therapy and defective non-replicative vectors for gene therapy. Vectors from each class can accommodate ≥30 kb of inserts, have been approved clinically, and demonstrate a relatively benign safety profile. Despite oncolytic HSV (oHSV) replication in tumors and elicited immune responses, the virus is well tolerated in cancer patients. Current non-replicative vectors elicit only limited immune responses. Seropositivity and immune responses against HSV-1 do not eliminate either the vector or infected cells, and the vectors can therefore be re-administered. In this review we highlight vectors that have been translated to the clinic and host-virus immune interactions that impact on the safety and efficacy of HSVs.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-29DOI: 10.1016/j.molmed.2024.07.007
Agnes Ayton
{"title":"Advancements in intensive eating disorder treatments: the benefit of CBT-E and integrated care models.","authors":"Agnes Ayton","doi":"10.1016/j.molmed.2024.07.007","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.07.007","url":null,"abstract":"","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856571","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 : 2024-07-27DOI: 10.1016/j.molmed.2024.07.006
Philippe Codron, Stéphanie Millecamps, Philippe Corcia
The identification of biomarkers for amyotrophic lateral sclerosis (ALS) is a central issue in disease research. In a recent article, Chatterjee et al. show that blood extracellular vesicles (EVs) with high levels of transactive response DNA-binding protein 43 (TDP-43) accurately discriminate patients with ALS from controls and correlate with disease severity, providing a promising biomarker for early diagnosis and monitoring.
确定肌萎缩性脊髓侧索硬化症(ALS)的生物标志物是疾病研究的核心问题。Chatterjee 等人在最近的一篇文章中指出,血液细胞外囊泡 (EVs) 中含有高水平的转录反应 DNA 结合蛋白 43 (TDP-43),能准确地区分 ALS 患者和对照组,并与疾病严重程度相关,为早期诊断和监测提供了一种很有前景的生物标记物。
{"title":"EVolution in ALS diagnosis: molecular markers in extracellular vesicles.","authors":"Philippe Codron, Stéphanie Millecamps, Philippe Corcia","doi":"10.1016/j.molmed.2024.07.006","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.07.006","url":null,"abstract":"<p><p>The identification of biomarkers for amyotrophic lateral sclerosis (ALS) is a central issue in disease research. In a recent article, Chatterjee et al. show that blood extracellular vesicles (EVs) with high levels of transactive response DNA-binding protein 43 (TDP-43) accurately discriminate patients with ALS from controls and correlate with disease severity, providing a promising biomarker for early diagnosis and monitoring.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789095","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 : 2024-07-27DOI: 10.1016/j.molmed.2024.07.005
Hippokratis Kiaris
Historical reasons resulted in the almost exclusive use of a few species, most prominently Mus musculus, as the mainstream models in biomedical research. This selection was not based on Mus's distinctive relevance to human disease but rather to the pre-existing availability of resources and tools for the species that were used as models, which has enabled their adoption for research in health sciences. Unless the utilization and range of nontraditional research models expand considerably, progress in biomedical research will remain restricted within the trajectory that has been set by the existing models and their ability to provide clinically relevant information.
{"title":"Nontraditional models as research tools: the road not taken.","authors":"Hippokratis Kiaris","doi":"10.1016/j.molmed.2024.07.005","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.07.005","url":null,"abstract":"<p><p>Historical reasons resulted in the almost exclusive use of a few species, most prominently Mus musculus, as the mainstream models in biomedical research. This selection was not based on Mus's distinctive relevance to human disease but rather to the pre-existing availability of resources and tools for the species that were used as models, which has enabled their adoption for research in health sciences. Unless the utilization and range of nontraditional research models expand considerably, progress in biomedical research will remain restricted within the trajectory that has been set by the existing models and their ability to provide clinically relevant information.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789096","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 : 2024-07-24DOI: 10.1016/j.molmed.2024.07.001
Peiwei Chai, Fei Zhao, Renbing Jia, Xiangtian Zhou, Xianqun Fan
Lactylation, a post-translational modification (PTM) induced by lactate, has crucial roles in the regulation of transcription, DNA repair, and mitochondrial metabolism. Here, we discuss the role of lactate/lactylation signaling in regulating eye morphogenesis and retinal homeostasis, as well as various ophthalmic disorders, such as myopia, intraocular malignancies, and retinal angiogenesis.
{"title":"Lactate/lactylation in ocular development and diseases.","authors":"Peiwei Chai, Fei Zhao, Renbing Jia, Xiangtian Zhou, Xianqun Fan","doi":"10.1016/j.molmed.2024.07.001","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.07.001","url":null,"abstract":"<p><p>Lactylation, a post-translational modification (PTM) induced by lactate, has crucial roles in the regulation of transcription, DNA repair, and mitochondrial metabolism. Here, we discuss the role of lactate/lactylation signaling in regulating eye morphogenesis and retinal homeostasis, as well as various ophthalmic disorders, such as myopia, intraocular malignancies, and retinal angiogenesis.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761116","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 : 2024-07-15DOI: 10.1016/j.molmed.2024.06.009
Binghao Zhao, Longping Yao, Maryam Hatami, Wenbin Ma, Thomas Skutella
Glioma, the most common primary malignant tumor in the central nervous system (CNS), lacks effective treatments, and >60% of cases are glioblastoma (GBM), the most aggressive form. Despite advances in immunotherapy, GBM remains highly resistant. Approaches that target tumor antigens expedite the development of immunotherapies, including personalized tumor-specific vaccines, patient-specific target selection, dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) and T cell receptor (TCR) T cells. Recent studies show promising results in treating GBM and lower-grade glioma (LGG), fostering hope for future immunotherapy. This review discusses tumor vaccines against glioma, preclinical models in immunological research, and the role of CD4+ T cells in vaccine-induced antitumor immunity. We also summarize clinical approaches, challenges, and future research for creating more effective vaccines.
胶质瘤是中枢神经系统(CNS)中最常见的原发性恶性肿瘤,但缺乏有效的治疗方法,60%以上的病例为胶质母细胞瘤(GBM),这是一种侵袭性最强的肿瘤。尽管免疫疗法取得了进展,但胶质母细胞瘤的抗药性仍然很强。针对肿瘤抗原的方法加快了免疫疗法的发展,包括个性化肿瘤特异性疫苗、患者特异性靶点选择、树突状细胞(DC)疫苗以及嵌合抗原受体(CAR)和 T 细胞受体(TCR)T 细胞。最近的研究表明,治疗 GBM 和低级别胶质瘤 (LGG) 的效果很好,这为未来的免疫疗法带来了希望。本综述讨论了针对胶质瘤的肿瘤疫苗、免疫学研究中的临床前模型以及 CD4+ T 细胞在疫苗诱导的抗肿瘤免疫中的作用。我们还总结了临床方法、挑战和未来研究,以创造更有效的疫苗。
{"title":"Vaccine-based immunotherapy and related preclinical models for glioma.","authors":"Binghao Zhao, Longping Yao, Maryam Hatami, Wenbin Ma, Thomas Skutella","doi":"10.1016/j.molmed.2024.06.009","DOIUrl":"10.1016/j.molmed.2024.06.009","url":null,"abstract":"<p><p>Glioma, the most common primary malignant tumor in the central nervous system (CNS), lacks effective treatments, and >60% of cases are glioblastoma (GBM), the most aggressive form. Despite advances in immunotherapy, GBM remains highly resistant. Approaches that target tumor antigens expedite the development of immunotherapies, including personalized tumor-specific vaccines, patient-specific target selection, dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) and T cell receptor (TCR) T cells. Recent studies show promising results in treating GBM and lower-grade glioma (LGG), fostering hope for future immunotherapy. This review discusses tumor vaccines against glioma, preclinical models in immunological research, and the role of CD4<sup>+</sup> T cells in vaccine-induced antitumor immunity. We also summarize clinical approaches, challenges, and future research for creating more effective vaccines.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627745","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 : 2024-07-13DOI: 10.1016/j.molmed.2024.07.002
Bettina Schock, Steven O'Reilly
Senescence is associated with multiple morbidities and therapeutic targeting of these cells is a key aim. In a recent study, Katsuumi et al. found that targeting sodium-glucose co-transporter 2 (SGLT2) promoted immune clearance of senescent cells via programmed cell death-1 ligand (PD-L1) suppression, thus promoting immunosurveillance. This could have profound implications for many age-related diseases, including cancer and frailty.
{"title":"Striking senescence with sodium transporter inhibition.","authors":"Bettina Schock, Steven O'Reilly","doi":"10.1016/j.molmed.2024.07.002","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.07.002","url":null,"abstract":"<p><p>Senescence is associated with multiple morbidities and therapeutic targeting of these cells is a key aim. In a recent study, Katsuumi et al. found that targeting sodium-glucose co-transporter 2 (SGLT2) promoted immune clearance of senescent cells via programmed cell death-1 ligand (PD-L1) suppression, thus promoting immunosurveillance. This could have profound implications for many age-related diseases, including cancer and frailty.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617167","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 : 2024-07-13DOI: 10.1016/j.molmed.2024.06.012
Francisco Romo-Nava
Circadian system disruption is an essential but poorly understood feature of bipolar disorder (BD) and associated comorbidities. This forum article summarizes current evidence regarding the emerging concept of circadian phase instability (CPI) as a neglected phenomenon with possibly unique features in BD that could be harnessed to develop individually tailored chronobiological interventions.
{"title":"Circadian phase instability in bipolar disorder: a neglected essence.","authors":"Francisco Romo-Nava","doi":"10.1016/j.molmed.2024.06.012","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.06.012","url":null,"abstract":"<p><p>Circadian system disruption is an essential but poorly understood feature of bipolar disorder (BD) and associated comorbidities. This forum article summarizes current evidence regarding the emerging concept of circadian phase instability (CPI) as a neglected phenomenon with possibly unique features in BD that could be harnessed to develop individually tailored chronobiological interventions.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617166","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 : 2024-07-13DOI: 10.1016/j.molmed.2024.06.011
Knut Dahl-Jørgensen
Type 1 diabetes (T1D), a severe disease requiring intensive insulin treatment, carries an increased risk for complications and reduced lifespan. Certain viruses have been implicated in T1D's etiology, with 'live', replicating enteroviruses (EVs) recently found in the pancreas at diagnosis. This discovery prompted a trial to slow down disease progression using antiviral drugs. A 6-month treatment combining pleconaril and ribavirin in new-onset T1D patients preserved residual insulin production after 1 year, unlike placebo. The results support the theory that viruses may cause T1D in genetically susceptible individuals. A low-grade, persistent viral infection may initiate a cascade of pathogenic mechanisms initially involving the innate immune system, inducing β-cell stress and neoantigen release, leading to autoimmunity, and eventually the destruction of insulin-producing β-cells.
{"title":"Virus as the cause of type 1 diabetes.","authors":"Knut Dahl-Jørgensen","doi":"10.1016/j.molmed.2024.06.011","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.06.011","url":null,"abstract":"<p><p>Type 1 diabetes (T1D), a severe disease requiring intensive insulin treatment, carries an increased risk for complications and reduced lifespan. Certain viruses have been implicated in T1D's etiology, with 'live', replicating enteroviruses (EVs) recently found in the pancreas at diagnosis. This discovery prompted a trial to slow down disease progression using antiviral drugs. A 6-month treatment combining pleconaril and ribavirin in new-onset T1D patients preserved residual insulin production after 1 year, unlike placebo. The results support the theory that viruses may cause T1D in genetically susceptible individuals. A low-grade, persistent viral infection may initiate a cascade of pathogenic mechanisms initially involving the innate immune system, inducing β-cell stress and neoantigen release, leading to autoimmunity, and eventually the destruction of insulin-producing β-cells.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604195","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}