Pub Date : 2024-07-05DOI: 10.1038/d41573-024-00116-1
Asher Mullard
{"title":"FDA approves third anti-amyloid antibody for Alzheimer disease","authors":"Asher Mullard","doi":"10.1038/d41573-024-00116-1","DOIUrl":"10.1038/d41573-024-00116-1","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 8","pages":"571-571"},"PeriodicalIF":122.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538284","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 : 2024-07-04DOI: 10.1038/s41573-024-00977-6
P. R. Cullis, P. L. Felgner
Delivery of genetic information to the interior of target cells in vivo has been a major challenge facing gene therapies. This barrier is now being overcome, owing in part to dramatic advances made by lipid-based systems that have led to lipid nanoparticles (LNPs) that enable delivery of nucleic acid-based vaccines and therapeutics. Examples include the clinically approved COVID-19 LNP mRNA vaccines and Onpattro (patisiran), an LNP small interfering RNA therapeutic to treat transthyretin-induced amyloidosis (hATTR). In addition, a host of promising LNP-enabled vaccines and gene therapies are in clinical development. Here, we trace this success to two streams of research conducted over the past 60 years: the discovery of the transfection properties of lipoplexes composed of positively charged cationic lipids complexed with nucleic acid cargos and the development of lipid nanoparticles using ionizable cationic lipids. The fundamental insights gained from these two streams of research offer potential delivery solutions for most forms of gene therapies. Lipid nanoparticle-based systems are increasingly being utilized for the delivery of nucleic acid-based vaccines and therapeutics. In this Perspective, Cullis and Felgner trace the evolution of these systems over the past 60 years and discuss future prospects for LNP-enabled gene therapies.
{"title":"The 60-year evolution of lipid nanoparticles for nucleic acid delivery","authors":"P. R. Cullis, P. L. Felgner","doi":"10.1038/s41573-024-00977-6","DOIUrl":"10.1038/s41573-024-00977-6","url":null,"abstract":"Delivery of genetic information to the interior of target cells in vivo has been a major challenge facing gene therapies. This barrier is now being overcome, owing in part to dramatic advances made by lipid-based systems that have led to lipid nanoparticles (LNPs) that enable delivery of nucleic acid-based vaccines and therapeutics. Examples include the clinically approved COVID-19 LNP mRNA vaccines and Onpattro (patisiran), an LNP small interfering RNA therapeutic to treat transthyretin-induced amyloidosis (hATTR). In addition, a host of promising LNP-enabled vaccines and gene therapies are in clinical development. Here, we trace this success to two streams of research conducted over the past 60 years: the discovery of the transfection properties of lipoplexes composed of positively charged cationic lipids complexed with nucleic acid cargos and the development of lipid nanoparticles using ionizable cationic lipids. The fundamental insights gained from these two streams of research offer potential delivery solutions for most forms of gene therapies. Lipid nanoparticle-based systems are increasingly being utilized for the delivery of nucleic acid-based vaccines and therapeutics. In this Perspective, Cullis and Felgner trace the evolution of these systems over the past 60 years and discuss future prospects for LNP-enabled gene therapies.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 9","pages":"709-722"},"PeriodicalIF":122.7,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141534881","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 : 2024-07-01DOI: 10.1038/s41573-024-00974-9
Ningqiang Gong, Mohamad-Gabriel Alameh, Rakan El-Mayta, Lulu Xue, Drew Weissman, Michael J. Mitchell
In situ cancer vaccination refers to any approach that exploits tumour antigens available at a tumour site to induce tumour-specific adaptive immune responses. These approaches hold great promise for the treatment of many solid tumours, with numerous candidate drugs under preclinical or clinical evaluation and several products already approved. However, there are challenges in the development of effective in situ cancer vaccines. For example, inadequate release of tumour antigens from tumour cells limits antigen uptake by immune cells; insufficient antigen processing by antigen-presenting cells restricts the generation of antigen-specific T cell responses; and the suppressive immune microenvironment of the tumour leads to exhaustion and death of effector cells. Rationally designed delivery technologies such as lipid nanoparticles, hydrogels, scaffolds and polymeric nanoparticles are uniquely suited to overcome these challenges through the targeted delivery of therapeutics to tumour cells, immune cells or the extracellular matrix. Here, we discuss delivery technologies that have the potential to reduce various clinical barriers for in situ cancer vaccines. We also provide our perspective on this emerging field that lies at the interface of cancer vaccine biology and delivery technologies. In situ cancer vaccines generate tumour-specific T cell responses and hold promise for the treatment of solid tumours. This Review discusses drug delivery technologies such as lipid nanoparticles, hydrogels and scaffolds that are being developed to boost the antitumour immune effects of several types of in situ cancer vaccine.
癌症原位疫苗接种是指利用肿瘤部位的肿瘤抗原诱导肿瘤特异性适应性免疫反应的任何方法。这些方法在治疗许多实体瘤方面大有可为，许多候选药物正在进行临床前或临床评估，还有一些产品已经获得批准。然而，开发有效的原位癌症疫苗也面临着挑战。例如，肿瘤细胞对肿瘤抗原的释放不足限制了免疫细胞对抗原的吸收；抗原递呈细胞对抗原的处理不足限制了抗原特异性 T 细胞反应的产生；肿瘤的抑制性免疫微环境导致效应细胞衰竭和死亡。合理设计的递送技术，如脂质纳米颗粒、水凝胶、支架和聚合物纳米颗粒，通过向肿瘤细胞、免疫细胞或细胞外基质靶向递送治疗药物，是克服这些挑战的独特方法。在此，我们将讨论有可能减少原位癌症疫苗各种临床障碍的递送技术。我们还将对这一处于癌症疫苗生物学和递送技术交界处的新兴领域提出自己的看法。
{"title":"Enhancing in situ cancer vaccines using delivery technologies","authors":"Ningqiang Gong, Mohamad-Gabriel Alameh, Rakan El-Mayta, Lulu Xue, Drew Weissman, Michael J. Mitchell","doi":"10.1038/s41573-024-00974-9","DOIUrl":"10.1038/s41573-024-00974-9","url":null,"abstract":"In situ cancer vaccination refers to any approach that exploits tumour antigens available at a tumour site to induce tumour-specific adaptive immune responses. These approaches hold great promise for the treatment of many solid tumours, with numerous candidate drugs under preclinical or clinical evaluation and several products already approved. However, there are challenges in the development of effective in situ cancer vaccines. For example, inadequate release of tumour antigens from tumour cells limits antigen uptake by immune cells; insufficient antigen processing by antigen-presenting cells restricts the generation of antigen-specific T cell responses; and the suppressive immune microenvironment of the tumour leads to exhaustion and death of effector cells. Rationally designed delivery technologies such as lipid nanoparticles, hydrogels, scaffolds and polymeric nanoparticles are uniquely suited to overcome these challenges through the targeted delivery of therapeutics to tumour cells, immune cells or the extracellular matrix. Here, we discuss delivery technologies that have the potential to reduce various clinical barriers for in situ cancer vaccines. We also provide our perspective on this emerging field that lies at the interface of cancer vaccine biology and delivery technologies. In situ cancer vaccines generate tumour-specific T cell responses and hold promise for the treatment of solid tumours. This Review discusses drug delivery technologies such as lipid nanoparticles, hydrogels and scaffolds that are being developed to boost the antitumour immune effects of several types of in situ cancer vaccine.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 8","pages":"607-625"},"PeriodicalIF":122.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477027","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 : 2024-06-27DOI: 10.1038/d41573-024-00114-3
Asher Mullard
Sharon Barr, head of BioPharmaceuticals R&D at AstraZeneca, discusses her chronic disease research priorities, including the need for new diagnostic tools, fixed-dose drugs and a better understanding of disease biology. Sharon Barr, head of BioPharmaceuticals R&D at AstraZeneca, discusses her chronic disease research priorities, including the need for new diagnostic tools, fixed-dose drugs and a better understanding of disease biology.
{"title":"When chronic and rare disease worlds converge","authors":"Asher Mullard","doi":"10.1038/d41573-024-00114-3","DOIUrl":"10.1038/d41573-024-00114-3","url":null,"abstract":"Sharon Barr, head of BioPharmaceuticals R&D at AstraZeneca, discusses her chronic disease research priorities, including the need for new diagnostic tools, fixed-dose drugs and a better understanding of disease biology. Sharon Barr, head of BioPharmaceuticals R&D at AstraZeneca, discusses her chronic disease research priorities, including the need for new diagnostic tools, fixed-dose drugs and a better understanding of disease biology.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 9","pages":"654-655"},"PeriodicalIF":122.7,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141462382","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 : 2024-06-25DOI: 10.1038/d41573-024-00109-0
Asher Mullard
Jude Samulski, former CSO and co-founder of AskBio, discusses the future of gene therapy for complex and common diseases, including Parkinson disease and congestive heart failure. Jude Samulski, former CSO and co-founder of AskBio, discusses the future of gene therapy for complex and common diseases, including Parkinson disease and congestive heart failure.
{"title":"Gene therapies start the climb from rare disease base camps to common disease peaks","authors":"Asher Mullard","doi":"10.1038/d41573-024-00109-0","DOIUrl":"10.1038/d41573-024-00109-0","url":null,"abstract":"Jude Samulski, former CSO and co-founder of AskBio, discusses the future of gene therapy for complex and common diseases, including Parkinson disease and congestive heart failure. Jude Samulski, former CSO and co-founder of AskBio, discusses the future of gene therapy for complex and common diseases, including Parkinson disease and congestive heart failure.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 8","pages":"574-576"},"PeriodicalIF":122.7,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141448218","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}
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