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Nature Reviews. Drug Discovery最新文献

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Harnessing the biology of regulatory T cells to treat disease 利用调节性T细胞的生物学特性来治疗疾病
IF 122.7 1区 医学
Nature Reviews. Drug Discovery Pub Date : 2024-12-16 DOI: 10.1038/s41573-024-01089-x
Christine M. Wardell, Dominic A. Boardman, Megan K. Levings
{"title":"Harnessing the biology of regulatory T cells to treat disease","authors":"Christine M. Wardell, Dominic A. Boardman, Megan K. Levings","doi":"10.1038/s41573-024-01089-x","DOIUrl":"10.1038/s41573-024-01089-x","url":null,"abstract":"Regulatory T (Treg) cells are a suppressive subset of CD4+ T cells that maintain immune homeostasis and restrain inflammation. Three decades after their discovery, the promise of strategies to harness Treg cells for therapy has never been stronger. Multiple clinical trials seeking to enhance endogenous Treg cells or deliver them as a cell-based therapy have been performed and hint at signs of success, as well as to important limitations and unanswered questions. Strategies to deplete Treg cells in cancer are also in active clinical testing. Furthermore, multi-dimensional methods to interrogate the biology of Treg cells are leading to a refined understanding of Treg cell biology and new approaches to harness tissue-specific functions for therapy. A new generation of Treg cell clinical trials is now being fuelled by advances in nanomedicine and synthetic biology, seeking more precise ways to tailor Treg cell function. This Review will discuss recent advances in our understanding of human Treg cell biology, with a focus on mechanisms of action and strategies to assess outcomes of Treg cell-targeted therapies. It highlights results from recent clinical trials aiming to enhance or inhibit Treg cell activity in a variety of diseases, including allergy, transplantation, autoimmunity and cancer, and discusses ongoing strategies to refine these approaches. Regulatory T cells keep the immune system in check to maintain homeostasis and restrain inflammation. This Review discusses strategies to harness these cells therapeutically for autoimmunity, transplant tolerance or cancer, for example, by boosting their endogenous function, depleting them or administering them as engineered cell-based therapies.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"24 2","pages":"93-111"},"PeriodicalIF":122.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825691","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
IRDiRC perspectives on the application of digital biomarkers in therapeutic development for rare diseases IRDiRC 关于在罕见病治疗开发中应用数字生物标记的观点
IF 122.7 1区 医学
Nature Reviews. Drug Discovery Pub Date : 2024-12-16 DOI: 10.1038/d41573-024-00196-z
Rajesh Krishna,  Anneliene H. Jonker,  Thomas Morel,  Ken Sakushima,  Anna M. G. Pasmooij,  Daniel O’Connor
{"title":"IRDiRC perspectives on the application of digital biomarkers in therapeutic development for rare diseases","authors":"Rajesh Krishna, \u0000 Anneliene H. Jonker, \u0000 Thomas Morel, \u0000 Ken Sakushima, \u0000 Anna M. G. Pasmooij, \u0000 Daniel O’Connor","doi":"10.1038/d41573-024-00196-z","DOIUrl":"10.1038/d41573-024-00196-z","url":null,"abstract":"New approaches are needed to streamline clinical trials of drugs for patients with rare diseases. Digital biomarkers offer one such approach, but several challenges must be addressed to realize their potential. New approaches are needed to streamline clinical trials of drugs for patients with rare diseases. Digital biomarkers offer one such approach, but several challenges must be addressed to realize their potential.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"24 4","pages":"233-234"},"PeriodicalIF":122.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825692","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
NaV1.8 inhibitor poised to provide opioid-free pain relief NaV1.8抑制剂有望提供无阿片类药物疼痛缓解
IF 122.7 1区 医学
Nature Reviews. Drug Discovery Pub Date : 2024-12-12 DOI: 10.1038/d41573-024-00203-3
Katie Kingwell
{"title":"NaV1.8 inhibitor poised to provide opioid-free pain relief","authors":"Katie Kingwell","doi":"10.1038/d41573-024-00203-3","DOIUrl":"10.1038/d41573-024-00203-3","url":null,"abstract":"Vertex’s first-in-class suzetrigine could soon usher in a new class of analgesic. Vertex’s first-in-class suzetrigine could soon usher in a new class of analgesic.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"24 1","pages":"3-5"},"PeriodicalIF":122.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809770","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
Targeting metabolic dysfunction of CD8 T cells and natural killer cells in cancer 靶向CD8 T细胞和自然杀伤细胞在肿瘤中的代谢功能障碍
IF 122.7 1区 医学
Nature Reviews. Drug Discovery Pub Date : 2024-12-12 DOI: 10.1038/s41573-024-01098-w
Sébastien Viel, Eric Vivier, Thierry Walzer, Antoine Marçais
{"title":"Targeting metabolic dysfunction of CD8 T cells and natural killer cells in cancer","authors":"Sébastien Viel, Eric Vivier, Thierry Walzer, Antoine Marçais","doi":"10.1038/s41573-024-01098-w","DOIUrl":"10.1038/s41573-024-01098-w","url":null,"abstract":"The importance of metabolic pathways in regulating immune responses is now well established, and a mapping of the bioenergetic metabolism of different immune cell types is under way. CD8 T cells and natural killer (NK) cells contribute to cancer immunosurveillance through their cytotoxic functions and secretion of cytokines and chemokines, complementing each other in target recognition mechanisms. Several immunotherapies leverage these cell types by either stimulating their activity or redirecting their specificity against tumour cells. However, the anticancer activity of CD8 T cells and NK cells is rapidly diminished in the tumour microenvironment, closely linked to a decline in their metabolic capacities. Various strategies have been developed to restore cancer immunosurveillance, including targeting bioenergetic metabolism or genetic engineering. This Review provides an overview of metabolic dysfunction in CD8 T cells and NK cells within the tumour microenvironment, highlighting current therapies aiming to overcome these issues. CD8 T cells and natural killer (NK) cells play a key role in cancer immunosurveillance. However, their anticancer activity is rapidly diminished in the tumour microenvironment, associated with a decline in their metabolic function. This Review provides an overview of metabolic programmes in CD8 T cells and NK cells, discusses the dysfunction that can occur in cancer, and assesses therapeutic strategies to overcome this.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"24 3","pages":"190-208"},"PeriodicalIF":122.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815515","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
Upcoming FDA approval decisions in Q1 2025 FDA将于2025年第一季度做出批准决定
IF 122.7 1区 医学
Nature Reviews. Drug Discovery Pub Date : 2024-12-11 DOI: 10.1038/d41573-024-00202-4
Kaniaw Dilzer
{"title":"Upcoming FDA approval decisions in Q1 2025","authors":"Kaniaw Dilzer","doi":"10.1038/d41573-024-00202-4","DOIUrl":"10.1038/d41573-024-00202-4","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"24 1","pages":"9-9"},"PeriodicalIF":122.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805115","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
Top product forecasts for 2025 2025年的顶级产品预测
IF 122.7 1区 医学
Nature Reviews. Drug Discovery Pub Date : 2024-12-10 DOI: 10.1038/d41573-024-00199-w
Paul Verdin
{"title":"Top product forecasts for 2025","authors":"Paul Verdin","doi":"10.1038/d41573-024-00199-w","DOIUrl":"10.1038/d41573-024-00199-w","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"24 1","pages":"8-8"},"PeriodicalIF":122.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797215","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
Can non-canonical amino acids open up non-canonical drug discovery opportunities? 非规范氨基酸能打开非规范药物发现的机会吗？
IF 122.7 1区 医学
Nature Reviews. Drug Discovery Pub Date : 2024-12-09 DOI: 10.1038/d41573-024-00201-5
Asher Mullard
{"title":"Can non-canonical amino acids open up non-canonical drug discovery opportunities?","authors":"Asher Mullard","doi":"10.1038/d41573-024-00201-5","DOIUrl":"10.1038/d41573-024-00201-5","url":null,"abstract":"Jason Chin, head of Cambridge’s Centre for Chemical & Synthetic Biology and CSO of Constructive Bio, discusses the role for unnatural amino acids in biologic therapies. Jason Chin, head of Cambridge’s Centre for Chemical & Synthetic Biology and CSO of Constructive Bio, discusses the role for unnatural amino acids in biologic therapies.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"24 1","pages":"10-11"},"PeriodicalIF":122.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793811","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
Showing tau the exit 显示出口
IF 122.7 1区 医学
Nature Reviews. Drug Discovery Pub Date : 2024-12-05 DOI: 10.1038/d41573-024-00200-6
M. Teresa Villanueva
{"title":"Showing tau the exit","authors":"M. Teresa Villanueva","doi":"10.1038/d41573-024-00200-6","DOIUrl":"10.1038/d41573-024-00200-6","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"24 1","pages":"16-16"},"PeriodicalIF":122.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142777214","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
Covalent inhibitor engages oncogenic AKT kinase 共价抑制剂参与致癌AKT激酶
IF 122.7 1区 医学
Nature Reviews. Drug Discovery Pub Date : 2024-12-03 DOI: 10.1038/d41573-024-00197-y
Alex Eccleston
{"title":"Covalent inhibitor engages oncogenic AKT kinase","authors":"Alex Eccleston","doi":"10.1038/d41573-024-00197-y","DOIUrl":"10.1038/d41573-024-00197-y","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"24 1","pages":"16-16"},"PeriodicalIF":122.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760432","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
FDA approves first menin inhibitor, for acute leukaemia FDA批准首个治疗急性白血病的menin抑制剂
IF 122.7 1区 医学
Nature Reviews. Drug Discovery Pub Date : 2024-12-03 DOI: 10.1038/d41573-024-00198-x
Asher Mullard
{"title":"FDA approves first menin inhibitor, for acute leukaemia","authors":"Asher Mullard","doi":"10.1038/d41573-024-00198-x","DOIUrl":"10.1038/d41573-024-00198-x","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"24 1","pages":"7-7"},"PeriodicalIF":122.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763758","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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