Pub Date : 2024-10-30DOI: 10.1038/d41573-024-00175-4
Asher Mullard
{"title":"FDA approves first anti-TFPI antibody for haemophilia A and B","authors":"Asher Mullard","doi":"10.1038/d41573-024-00175-4","DOIUrl":"10.1038/d41573-024-00175-4","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 12","pages":"884-884"},"PeriodicalIF":122.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541943","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 : 2024-10-24DOI: 10.1038/s41573-024-01053-9
Michael Croft, Shahram Salek-Ardakani, Carl F. Ware
The first anti-tumour necrosis factor (TNF) monoclonal antibody, infliximab (Remicade), celebrated its 25th anniversary of FDA approval in 2023. Inhibitors of TNF have since proved clinically efficacious at reducing inflammation associated with several autoimmune diseases, including rheumatoid arthritis, psoriasis and Crohn’s disease. The success of TNF inhibitors raised unrealistic expectations for targeting other members of the TNF superfamily (TNFSF) of ligands and their receptors, with difficulties in part related to their more limited, variable expression and potential redundancy. However, there has been a resurgence of interest and investment, with many of these cytokines or their cognate receptors now under clinical investigation as targets for modulation of autoimmune and inflammatory diseases, as well as cancer. This Review assesses TNFSF-targeted biologics currently in clinical development for immune system-related diseases, highlighting ongoing challenges and future directions. Members of the TNF superfamily (TNFSF) of ligands and their receptors have emerged as promising targets in the treatment of autoimmune diseases and cancer, with several biologics gaining FDA approval. However, there are still many hurdles to realizing the true potential of targeting these superfamilies. This Review assesses past and ongoing clinical trials of agents modulating TNFSF ligands or receptors, highlighting ongoing challenges and future opportunities.
{"title":"Targeting the TNF and TNFR superfamilies in autoimmune disease and cancer","authors":"Michael Croft, Shahram Salek-Ardakani, Carl F. Ware","doi":"10.1038/s41573-024-01053-9","DOIUrl":"10.1038/s41573-024-01053-9","url":null,"abstract":"The first anti-tumour necrosis factor (TNF) monoclonal antibody, infliximab (Remicade), celebrated its 25th anniversary of FDA approval in 2023. Inhibitors of TNF have since proved clinically efficacious at reducing inflammation associated with several autoimmune diseases, including rheumatoid arthritis, psoriasis and Crohn’s disease. The success of TNF inhibitors raised unrealistic expectations for targeting other members of the TNF superfamily (TNFSF) of ligands and their receptors, with difficulties in part related to their more limited, variable expression and potential redundancy. However, there has been a resurgence of interest and investment, with many of these cytokines or their cognate receptors now under clinical investigation as targets for modulation of autoimmune and inflammatory diseases, as well as cancer. This Review assesses TNFSF-targeted biologics currently in clinical development for immune system-related diseases, highlighting ongoing challenges and future directions. Members of the TNF superfamily (TNFSF) of ligands and their receptors have emerged as promising targets in the treatment of autoimmune diseases and cancer, with several biologics gaining FDA approval. However, there are still many hurdles to realizing the true potential of targeting these superfamilies. This Review assesses past and ongoing clinical trials of agents modulating TNFSF ligands or receptors, highlighting ongoing challenges and future opportunities.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 12","pages":"939-961"},"PeriodicalIF":122.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488776","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 : 2024-10-22DOI: 10.1038/d41573-024-00172-7
Asher Mullard
{"title":"FDA approves first claudin-18.2-targeted antibody for gastric cancer","authors":"Asher Mullard","doi":"10.1038/d41573-024-00172-7","DOIUrl":"10.1038/d41573-024-00172-7","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 12","pages":"884-884"},"PeriodicalIF":122.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486849","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 : 2024-10-21DOI: 10.1038/s41573-024-01041-z
Akash Gupta, Arnab Rudra, Kaelan Reed, Robert Langer, Daniel G. Anderson
Vaccines play a critical role in the prevention of life-threatening infectious disease. However, the development of effective vaccines against many immune-evading pathogens such as HIV has proven challenging, and existing vaccines against some diseases such as tuberculosis and malaria have limited efficacy. The historically slow rate of vaccine development and limited pan-variant immune responses also limit existing vaccine utility against rapidly emerging and mutating pathogens such as influenza and SARS-CoV-2. Additionally, reactogenic effects can contribute to vaccine hesitancy, further undermining the ability of vaccination campaigns to generate herd immunity. These limitations are fuelling the development of novel vaccine technologies to more effectively combat infectious diseases. Towards this end, advances in vaccine delivery systems, adjuvants, antigens and other technologies are paving the way for the next generation of vaccines. This Review focuses on recent advances in synthetic vaccine systems and their associated challenges, highlighting innovation in the field of nano- and nucleic acid-based vaccines. Vaccines play a critical role in combating infectious diseases, but their development faces challenges related to suboptimal efficacy, reactogenicity, slow development and high cost. This Review assesses emerging vaccine technologies aiming to address these limitations, focusing on advances in antigen and adjuvant selection and design, and next-generation delivery systems.
{"title":"Advanced technologies for the development of infectious disease vaccines","authors":"Akash Gupta, Arnab Rudra, Kaelan Reed, Robert Langer, Daniel G. Anderson","doi":"10.1038/s41573-024-01041-z","DOIUrl":"10.1038/s41573-024-01041-z","url":null,"abstract":"Vaccines play a critical role in the prevention of life-threatening infectious disease. However, the development of effective vaccines against many immune-evading pathogens such as HIV has proven challenging, and existing vaccines against some diseases such as tuberculosis and malaria have limited efficacy. The historically slow rate of vaccine development and limited pan-variant immune responses also limit existing vaccine utility against rapidly emerging and mutating pathogens such as influenza and SARS-CoV-2. Additionally, reactogenic effects can contribute to vaccine hesitancy, further undermining the ability of vaccination campaigns to generate herd immunity. These limitations are fuelling the development of novel vaccine technologies to more effectively combat infectious diseases. Towards this end, advances in vaccine delivery systems, adjuvants, antigens and other technologies are paving the way for the next generation of vaccines. This Review focuses on recent advances in synthetic vaccine systems and their associated challenges, highlighting innovation in the field of nano- and nucleic acid-based vaccines. Vaccines play a critical role in combating infectious diseases, but their development faces challenges related to suboptimal efficacy, reactogenicity, slow development and high cost. This Review assesses emerging vaccine technologies aiming to address these limitations, focusing on advances in antigen and adjuvant selection and design, and next-generation delivery systems.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 12","pages":"914-938"},"PeriodicalIF":122.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452327","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 : 2024-10-18DOI: 10.1038/s41573-024-01051-x
Paul J. Carter, Valerie Quarmby
Remarkable progress has been made in recent decades in engineering antibodies and other protein therapeutics, including enhancements to existing functions as well as the advent of novel molecules that confer biological activities previously unknown in nature. These protein therapeutics have brought major benefits to patients across multiple areas of medicine. One major ongoing challenge is that protein therapeutics can elicit unwanted immune responses (immunogenicity) in treated patients, including the generation of anti-drug antibodies. In rare and unpredictable cases, anti-drug antibodies can seriously compromise therapeutic safety and/or efficacy. Systematic deconvolution of this immunogenicity problem is confounded by the complexity of its many contributing factors and the inherent limitations of available experimental and computational methods. Nevertheless, continued progress with the assessment and mitigation of immunogenicity risk at the preclinical stage has the potential to reduce the incidence and severity of clinical immunogenicity events. This Review focuses on identifying key unsolved anti-drug antibody-related challenges and offers some pragmatic approaches towards addressing them. Examples are drawn mainly from antibodies, given that the majority of available clinical data are from this class of protein therapeutics. Plausible and seemingly tractable solutions are in sight for some immunogenicity problems, whereas other challenges will likely require completely new approaches. Engineered protein therapeutics, including antibodies, are valuable drugs offering major health benefits, but they can elicit unwanted immune responses. This Review identifies key challenges in assessing and mitigating the risk of immunogenicity, particularly the generation of anti-drug antibodies, and suggests pragmatic steps to address them.
{"title":"Immunogenicity risk assessment and mitigation for engineered antibody and protein therapeutics","authors":"Paul J. Carter, Valerie Quarmby","doi":"10.1038/s41573-024-01051-x","DOIUrl":"10.1038/s41573-024-01051-x","url":null,"abstract":"Remarkable progress has been made in recent decades in engineering antibodies and other protein therapeutics, including enhancements to existing functions as well as the advent of novel molecules that confer biological activities previously unknown in nature. These protein therapeutics have brought major benefits to patients across multiple areas of medicine. One major ongoing challenge is that protein therapeutics can elicit unwanted immune responses (immunogenicity) in treated patients, including the generation of anti-drug antibodies. In rare and unpredictable cases, anti-drug antibodies can seriously compromise therapeutic safety and/or efficacy. Systematic deconvolution of this immunogenicity problem is confounded by the complexity of its many contributing factors and the inherent limitations of available experimental and computational methods. Nevertheless, continued progress with the assessment and mitigation of immunogenicity risk at the preclinical stage has the potential to reduce the incidence and severity of clinical immunogenicity events. This Review focuses on identifying key unsolved anti-drug antibody-related challenges and offers some pragmatic approaches towards addressing them. Examples are drawn mainly from antibodies, given that the majority of available clinical data are from this class of protein therapeutics. Plausible and seemingly tractable solutions are in sight for some immunogenicity problems, whereas other challenges will likely require completely new approaches. Engineered protein therapeutics, including antibodies, are valuable drugs offering major health benefits, but they can elicit unwanted immune responses. This Review identifies key challenges in assessing and mitigating the risk of immunogenicity, particularly the generation of anti-drug antibodies, and suggests pragmatic steps to address them.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 12","pages":"898-913"},"PeriodicalIF":122.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448125","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 : 2024-10-17DOI: 10.1038/d41573-024-00163-8
Luca Pozzetti, Michael P. East, Tuomo Laitinen, Christopher R. M. Asquith
{"title":"TLK2: a target for cancer and viral latency","authors":"Luca Pozzetti, \u0000 Michael P. East, \u0000 Tuomo Laitinen, \u0000 Christopher R. M. Asquith","doi":"10.1038/d41573-024-00163-8","DOIUrl":"10.1038/d41573-024-00163-8","url":null,"abstract":"","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 12","pages":"886-886"},"PeriodicalIF":122.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440838","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 : 2024-10-15DOI: 10.1038/d41573-024-00169-2
Asher Mullard
Jeanne Marrazzo, the director of the NIAID, discusses post-COVID pandemic preparedness, H5N1 avian flu and the tension between infectious disease protection versus profit. Jeanne Marrazzo, the director of the NIAID, discusses post-COVID pandemic preparedness, H5N1 avian flu and the tension between infectious disease protection versus profit.
{"title":"New eyes on the infectious disease prize","authors":"Asher Mullard","doi":"10.1038/d41573-024-00169-2","DOIUrl":"10.1038/d41573-024-00169-2","url":null,"abstract":"Jeanne Marrazzo, the director of the NIAID, discusses post-COVID pandemic preparedness, H5N1 avian flu and the tension between infectious disease protection versus profit. Jeanne Marrazzo, the director of the NIAID, discusses post-COVID pandemic preparedness, H5N1 avian flu and the tension between infectious disease protection versus profit.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 11","pages":"808-809"},"PeriodicalIF":122.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435975","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 : 2024-10-14DOI: 10.1038/d41573-024-00170-9
Asher Mullard
Clinic-ready molecular glues and heterobifunctional PROTAC drugs are taking targeted protein degradation into uncharted territory. Clinic-ready molecular glues and heterobifunctional PROTAC drugs are taking targeted protein degradation into uncharted territory.
可用于临床的分子粘合剂和异功能 PROTAC 药物正将靶向蛋白质降解带入未知领域。
{"title":"Protein degraders push into novel target space","authors":"Asher Mullard","doi":"10.1038/d41573-024-00170-9","DOIUrl":"10.1038/d41573-024-00170-9","url":null,"abstract":"Clinic-ready molecular glues and heterobifunctional PROTAC drugs are taking targeted protein degradation into uncharted territory. Clinic-ready molecular glues and heterobifunctional PROTAC drugs are taking targeted protein degradation into uncharted territory.","PeriodicalId":19068,"journal":{"name":"Nature Reviews. Drug Discovery","volume":"23 11","pages":"799-802"},"PeriodicalIF":122.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431491","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：