Pub Date : 2024-12-03DOI: 10.1016/j.copbio.2024.103230
Min Zheng , James Lloyd , Peter Wardrop , Haoran Duan , Tao Liu , Liu Ye , Bing-Jie Ni
Amid growing concerns over climate change, the need to reduce nitrous oxide (N2O) emissions from sewage treatment is more urgent than ever. Sewage treatment plants are significant sources of N2O due to its production as an intermediate in nitrification and its release into the air during aeration. Effective management of the nitrification process is therefore vital for controlling or eliminating these emissions. Despite substantial efforts to quantify and understand N2O emissions from sewage treatment, success in reducing them has been limited. This review discusses and proposes promising solutions for reducing N2O emissions in sewage treatment, evaluates the potential of various strategies, and identifies ways to accelerate their development and implementation.
{"title":"Path to zero emission of nitrous oxide in sewage treatment: is nitrification controllable or avoidable?","authors":"Min Zheng , James Lloyd , Peter Wardrop , Haoran Duan , Tao Liu , Liu Ye , Bing-Jie Ni","doi":"10.1016/j.copbio.2024.103230","DOIUrl":"10.1016/j.copbio.2024.103230","url":null,"abstract":"<div><div>Amid growing concerns over climate change, the need to reduce nitrous oxide (N<sub>2</sub>O) emissions from sewage treatment is more urgent than ever. Sewage treatment plants are significant sources of N<sub>2</sub>O due to its production as an intermediate in nitrification and its release into the air during aeration. Effective management of the nitrification process is therefore vital for controlling or eliminating these emissions. Despite substantial efforts to quantify and understand N<sub>2</sub>O emissions from sewage treatment, success in reducing them has been limited. This review discusses and proposes promising solutions for reducing N<sub>2</sub>O emissions in sewage treatment, evaluates the potential of various strategies, and identifies ways to accelerate their development and implementation.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"91 ","pages":"Article 103230"},"PeriodicalIF":7.1,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-30DOI: 10.1016/j.copbio.2024.103229
Daniel E M Saavedra , Federico Baltar
Multifunctional enzymes can significantly impact biotechnological applications by performing activities beyond their primary functions. This review explores the role of the multifunctionality of alkaline phosphatase, a key enzyme in the phosphorus cycle, focusing on the molecular mechanisms influencing its activity and its biotechnological potential. We argue that understanding these aspects can enhance the utility of alkaline phosphatase in research and industry, fostering innovations in enzyme engineering, environmental biotechnology, and metabolic engineering. By exploring enzyme promiscuity, we highlight alkaline phosphatase’s versatility, paving the way for advancements in sustainable agriculture, environmental remediation, and clinical diagnostics. Further research will unlock new applications and catalytic efficiencies, driving forward ecological and biotechnological progress.
{"title":"Multifunctionality of alkaline phosphatase in ecology and biotechnology","authors":"Daniel E M Saavedra , Federico Baltar","doi":"10.1016/j.copbio.2024.103229","DOIUrl":"10.1016/j.copbio.2024.103229","url":null,"abstract":"<div><div>Multifunctional enzymes can significantly impact biotechnological applications by performing activities beyond their primary functions. This review explores the role of the multifunctionality of alkaline phosphatase, a key enzyme in the phosphorus cycle, focusing on the molecular mechanisms influencing its activity and its biotechnological potential. We argue that understanding these aspects can enhance the utility of alkaline phosphatase in research and industry, fostering innovations in enzyme engineering, environmental biotechnology, and metabolic engineering. By exploring enzyme promiscuity, we highlight alkaline phosphatase’s versatility, paving the way for advancements in sustainable agriculture, environmental remediation, and clinical diagnostics. Further research will unlock new applications and catalytic efficiencies, driving forward ecological and biotechnological progress.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"91 ","pages":"Article 103229"},"PeriodicalIF":7.1,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-27DOI: 10.1016/j.copbio.2024.103225
Edward Apraku , McKenna Farmer , Chayse Lavallais , Danna A Soriano , Justin Notestein , Keith Tyo , Jennifer Dunn , William A Tarpeh , George F Wells
Recovering nitrogen (N) from wastewater is a potential avenue to reduce reliance on energy-intensive synthetic nitrogen fixation via Haber-Bosch and subsequent treatment of N-laden wastewaters through nitrification–denitrification. However, many technical and economic factors hinder widespread application of N recovery, particularly low N concentrations in municipal wastewater, paucity of high-efficiency separations technologies compatible with biological treatment, and suitable products and markets for recovered N. In this perspective, we contextualize the challenges of N recovery today, propose integrated biological and physicochemical technologies to improve selective and tunable N recovery, and propose an expanded product portfolio for recovered N products beyond fertilizers. We highlight cyanophycin, an N-rich biopolymer produced by a diverse range of bacteria, as a potential target for N bioconcentration and downstream recovery from municipal wastewater. This perspective emphasizes the equal importance of integrated biological systems, physicochemical separations, and market assessment in advancing nitrogen recovery from wastewater.
{"title":"Toward a circular nitrogen bioeconomy: integrating nitrogen bioconcentration, separations, and high-value products for nitrogen recovery","authors":"Edward Apraku , McKenna Farmer , Chayse Lavallais , Danna A Soriano , Justin Notestein , Keith Tyo , Jennifer Dunn , William A Tarpeh , George F Wells","doi":"10.1016/j.copbio.2024.103225","DOIUrl":"10.1016/j.copbio.2024.103225","url":null,"abstract":"<div><div>Recovering nitrogen (N) from wastewater is a potential avenue to reduce reliance on energy-intensive synthetic nitrogen fixation via Haber-Bosch and subsequent treatment of N-laden wastewaters through nitrification–denitrification. However, many technical and economic factors hinder widespread application of N recovery, particularly low N concentrations in municipal wastewater, paucity of high-efficiency separations technologies compatible with biological treatment, and suitable products and markets for recovered N. In this perspective, we contextualize the challenges of N recovery today, propose integrated biological and physicochemical technologies to improve selective and tunable N recovery, and propose an expanded product portfolio for recovered N products beyond fertilizers. We highlight cyanophycin, an N-rich biopolymer produced by a diverse range of bacteria, as a potential target for N bioconcentration and downstream recovery from municipal wastewater. This perspective emphasizes the equal importance of integrated biological systems, physicochemical separations, and market assessment in advancing nitrogen recovery from wastewater.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"91 ","pages":"Article 103225"},"PeriodicalIF":7.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-26DOI: 10.1016/j.copbio.2024.103228
Brian Senyange , Joshua Wesana , Guido Van Huylenbroeck , Xavier Gellynck , Hans De Steur
The growing global demand for sustainable and safe food is a major challenge that increases the need for advanced alternatives such as tissue engineering (TE). TE offers promising solutions by improving yields, nutritional value and resilience of crops while also producing cultivated meat that reduces the environmental impact of livestock farming. The market potential for TE in meat production is considerable, and significant growth is expected. However, the regulatory framework for these innovations is developing slowly, and approval procedures vary across regions. This overview critically assesses the current applications of TE in the agri-food sector, their socio-economic potential and the regulatory challenges. It emphasises the need for harmonised, flexible and adaptive policies to effectively integrate engineered foods into the market.
全球对可持续安全食品日益增长的需求是一项重大挑战，这也增加了对组织工程（TE）等先进替代品的需求。组织工程技术通过提高农作物的产量、营养价值和抗逆性，同时生产可减少畜牧业对环境影响的栽培肉类，提供了前景广阔的解决方案。组织工程技术在肉类生产中的市场潜力巨大，预计将出现大幅增长。然而，这些创新技术的监管框架发展缓慢，各地区的审批程序也不尽相同。本综述批判性地评估了 TE 目前在农业食品领域的应用、其社会经济潜力和监管挑战。它强调需要制定统一、灵活和适应性强的政策，以便将工程食品有效地融入市场。
{"title":"Tissue engineering in the agri-food industry: current status, socio-economic overview and regulatory compliance","authors":"Brian Senyange , Joshua Wesana , Guido Van Huylenbroeck , Xavier Gellynck , Hans De Steur","doi":"10.1016/j.copbio.2024.103228","DOIUrl":"10.1016/j.copbio.2024.103228","url":null,"abstract":"<div><div>The growing global demand for sustainable and safe food is a major challenge that increases the need for advanced alternatives such as tissue engineering (TE). TE offers promising solutions by improving yields, nutritional value and resilience of crops while also producing cultivated meat that reduces the environmental impact of livestock farming. The market potential for TE in meat production is considerable, and significant growth is expected. However, the regulatory framework for these innovations is developing slowly, and approval procedures vary across regions. This overview critically assesses the current applications of TE in the agri-food sector, their socio-economic potential and the regulatory challenges. It emphasises the need for harmonised, flexible and adaptive policies to effectively integrate engineered foods into the market.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"91 ","pages":"Article 103228"},"PeriodicalIF":7.1,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.copbio.2024.103221
Francesc Corbera-Rubio, Roos Goedhart, Michele Laureni, Mark CM van Loosdrecht, Doris van Halem
Gravity-driven sand filters are the dominant groundwater treatment technology for drinking water production. In the past, physicochemical reactions were often assumed to play the main role in the removal of contaminants, but recent breakthroughs showcase the vital role of microorganisms. In this Current Opinion, we thoroughly assess the current understanding of biology in sand filters and explore the potential benefits of shifting toward designs aimed at promoting biological reactions. We highlight the main bottlenecks and propose key areas to be explored toward the next generation of sustainable, resource-efficient groundwater biofilters.
{"title":"A biotechnological perspective on sand filtration for drinking water production","authors":"Francesc Corbera-Rubio, Roos Goedhart, Michele Laureni, Mark CM van Loosdrecht, Doris van Halem","doi":"10.1016/j.copbio.2024.103221","DOIUrl":"10.1016/j.copbio.2024.103221","url":null,"abstract":"<div><div>Gravity-driven sand filters are the dominant groundwater treatment technology for drinking water production. In the past, physicochemical reactions were often assumed to play the main role in the removal of contaminants, but recent breakthroughs showcase the vital role of microorganisms. In this <em>Current Opinion</em>, we thoroughly assess the current understanding of biology in sand filters and explore the potential benefits of shifting toward designs aimed at promoting biological reactions. We highlight the main bottlenecks and propose key areas to be explored toward the next generation of sustainable, resource-efficient groundwater biofilters.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103221"},"PeriodicalIF":7.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.copbio.2024.103226
Will J Brownlie , Peter Alexander , Dana Cordell , Mark Maslin , Genevieve S Metson , Mark A Sutton , Bryan M Spears
The dependence of countries on phosphorus fertilisers derived from phosphate rock to maintain crop yields and ensure food security is well established. Yet, exposure of national food systems to constrained reserves of phosphate rock and supply chain complexities still pose risks to farmers’ access to this critical nutrient in many countries. Whilst phosphorus scarcity can threaten food security, suboptimal fertiliser use and poor wastewater treatment can lead to pollution of freshwaters and coasts, causing eutrophication. This impacts biodiversity, drinking water and aquatic food production. In some countries, national plans targeting the recycling of phosphorus losses back into food production are being considered, offering environmental and socio-economic benefits. Here, we review the literature on assessing risks to food security and water quality associated with national reliance on phosphate rock as the primary source of phosphorus for fertilisers. The scientific community has developed data and tools to enable countries to assess exposure in food systems from phosphorus supply and management and in the environment from pollution. However, current assessment approaches often overlook economic vulnerability, a key gap that hinders our understanding of the urgency and severity of impacts from inaction. Exposure assessments could be used to develop National Sustainable Phosphorus Plans embedding priority actions and financial instruments across existing policy frameworks. Actions include identifying local to national sources and sites for phosphorus recycling, identifying catchments and ecosystems where the benefits of reducing phosphorus pollution are greatest, and establishing an infrastructure development plan to enable greater recycling and reduced pollution. We discuss four integrated actions that will enable countries to take the first steps towards a circular phosphorus economy in the context of a challenging global situation.
{"title":"National phosphorus planning for food and environmental security","authors":"Will J Brownlie , Peter Alexander , Dana Cordell , Mark Maslin , Genevieve S Metson , Mark A Sutton , Bryan M Spears","doi":"10.1016/j.copbio.2024.103226","DOIUrl":"10.1016/j.copbio.2024.103226","url":null,"abstract":"<div><div>The dependence of countries on phosphorus fertilisers derived from phosphate rock to maintain crop yields and ensure food security is well established. Yet, exposure of national food systems to constrained reserves of phosphate rock and supply chain complexities still pose risks to farmers’ access to this critical nutrient in many countries. Whilst phosphorus scarcity can threaten food security, suboptimal fertiliser use and poor wastewater treatment can lead to pollution of freshwaters and coasts, causing eutrophication. This impacts biodiversity, drinking water and aquatic food production. In some countries, national plans targeting the recycling of phosphorus losses back into food production are being considered, offering environmental and socio-economic benefits. Here, we review the literature on assessing risks to food security and water quality associated with national reliance on phosphate rock as the primary source of phosphorus for fertilisers. The scientific community has developed data and tools to enable countries to assess exposure in food systems from phosphorus supply and management and in the environment from pollution. However, current assessment approaches often overlook economic vulnerability, a key gap that hinders our understanding of the urgency and severity of impacts from inaction. Exposure assessments could be used to develop National Sustainable Phosphorus Plans embedding priority actions and financial instruments across existing policy frameworks. Actions include identifying local to national sources and sites for phosphorus recycling, identifying catchments and ecosystems where the benefits of reducing phosphorus pollution are greatest, and establishing an infrastructure development plan to enable greater recycling and reduced pollution. We discuss four integrated actions that will enable countries to take the first steps towards a circular phosphorus economy in the context of a challenging global situation.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103226"},"PeriodicalIF":7.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-05DOI: 10.1016/j.copbio.2024.103223
Anna Mei , Kevin P Letscher , Sai Reddy
Chimeric antigen receptor (CAR) T cells are a powerful treatment against hematologic cancers. The functional phenotype of a CAR-T cell is influenced by the domains that comprise the synthetic receptor. Typically, the potency of therapeutic CAR-T cell candidates is assessed by preclinical functional assays and mouse models (i.e. human tumor xenografts). However, to date, only a few sets of domains (e.g. CD8, CD28, 41BB) have been extensively tested in preclinical assays and human clinical studies. To characterize the efficiency of a CAR, different assays have been utilized to analyze T cell phenotypes, such as expansion, cytotoxicity, secretome, and persistence. However, each of these previous studies evaluated the importance of an assay differently, resulting in a wide range of functionally diverse CARs. In this review, we highlight recent (high-throughput) methods to analyze CAR domains and demonstrate their impact on inducing T cell phenotypes and activity. We also describe advances in computational methods and their potential for identifying CAR variants with enhanced properties. Finally, we reflect on the need for a standardized scoring system to support the clinical development of next-generation CARs.
嵌合抗原受体（CAR）T 细胞是一种治疗血液癌症的有效方法。CAR-T 细胞的功能表型受合成受体结构域的影响。通常，临床前功能测定和小鼠模型（即人类肿瘤异种移植）可评估候选 CAR-T 治疗细胞的效力。然而，迄今为止，只有少数几个结构域（如 CD8、CD28、41BB）在临床前试验和人体临床研究中进行了广泛测试。为了描述 CAR 的效率，人们采用了不同的检测方法来分析 T 细胞的表型，如扩增、细胞毒性、分泌组和持久性。然而，以往的这些研究对检测方法重要性的评估各不相同，因此产生了多种功能各异的 CAR。在这篇综述中，我们重点介绍了最近分析 CAR 结构域的（高通量）方法，并展示了它们对诱导 T 细胞表型和活性的影响。我们还介绍了计算方法的进展及其在鉴定具有增强特性的 CAR 变体方面的潜力。最后，我们探讨了建立标准化评分系统以支持下一代 CAR 临床开发的必要性。
{"title":"Engineering next-generation chimeric antigen receptor-T cells: recent breakthroughs and remaining challenges in design and screening of novel chimeric antigen receptor variants","authors":"Anna Mei , Kevin P Letscher , Sai Reddy","doi":"10.1016/j.copbio.2024.103223","DOIUrl":"10.1016/j.copbio.2024.103223","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR) T cells are a powerful treatment against hematologic cancers. The functional phenotype of a CAR-T cell is influenced by the domains that comprise the synthetic receptor. Typically, the potency of therapeutic CAR-T cell candidates is assessed by preclinical functional assays and mouse models (i.e. human tumor xenografts). However, to date, only a few sets of domains (e.g. CD8, CD28, 41BB) have been extensively tested in preclinical assays and human clinical studies. To characterize the efficiency of a CAR, different assays have been utilized to analyze T cell phenotypes, such as expansion, cytotoxicity, secretome, and persistence. However, each of these previous studies evaluated the importance of an assay differently, resulting in a wide range of functionally diverse CARs. In this review, we highlight recent (high-throughput) methods to analyze CAR domains and demonstrate their impact on inducing T cell phenotypes and activity. We also describe advances in computational methods and their potential for identifying CAR variants with enhanced properties. Finally, we reflect on the need for a standardized scoring system to support the clinical development of next-generation CARs.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103223"},"PeriodicalIF":7.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-05DOI: 10.1016/j.copbio.2024.103222
Christina F Webster , Won-Jun Kim , Gemma Reguera , Maren L Friesen , Haluk Beyenal
This review presents current knowledge on applying bioelectrochemical sensors to monitor soil fertility through microbial activity and discusses future perspectives. Soil microbial activity is considered an indicator of soil fertility due to the interconnected relationship between soil nutrient composition, microbiome, and plant productivity. Similarities between soils and bioelectrochemical reactors provide the foundation for the design of bioelectrochemical sensors driven by microorganisms enriched as electrochemically active biofilms on polarized electrodes. The biofilm can exchange electrons with electrodes and metabolites with the nearby microbiome to generate electrochemical signals that inform of microbiome functions and nutrient bioavailability. Such mechanisms can be harnessed as a bioelectrochemical sensor for proxy monitoring of soil fertility to address the need for real-time monitoring of soils.
{"title":"Review: can bioelectrochemical sensors be used to monitor soil microbiome activity and fertility?","authors":"Christina F Webster , Won-Jun Kim , Gemma Reguera , Maren L Friesen , Haluk Beyenal","doi":"10.1016/j.copbio.2024.103222","DOIUrl":"10.1016/j.copbio.2024.103222","url":null,"abstract":"<div><div>This review presents current knowledge on applying bioelectrochemical sensors to monitor soil fertility through microbial activity and discusses future perspectives. Soil microbial activity is considered an indicator of soil fertility due to the interconnected relationship between soil nutrient composition, microbiome, and plant productivity. Similarities between soils and bioelectrochemical reactors provide the foundation for the design of bioelectrochemical sensors driven by microorganisms enriched as electrochemically active biofilms on polarized electrodes. The biofilm can exchange electrons with electrodes and metabolites with the nearby microbiome to generate electrochemical signals that inform of microbiome functions and nutrient bioavailability. Such mechanisms can be harnessed as a bioelectrochemical sensor for proxy monitoring of soil fertility to address the need for real-time monitoring of soils.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103222"},"PeriodicalIF":7.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-04DOI: 10.1016/j.copbio.2024.103224
Lene S Høydahl , Gøril Berntzen, Geir Å Løset
A major prevailing challenge limiting our ability to fully harness the potential of the latest-generation therapeutic antibodies is the scarcity of clinically established disease-specific targets. A major next step forward will therefore be to expand this target space. The recent clinical success of immunotherapies such as adoptive T-cell transfer, immune checkpoint inhibition, and chimeric antigen receptor (CAR) T-cell therapy strongly supports focusing on the immunopeptidome of peptides presented by human leukocyte antigen (pHLA) that are normally surveilled by T-cell receptors (TCRs). Directing novel antibody development toward pHLA targets has given rise to TCR-like antibodies, which reached the clinic in 2020, as both bispecific T-cell engaging antibodies and the CARs of CAR-T cell therapies. In this review, we highlight recent advances in TCR-like antibodies, including therapeutic modalities, engineering strategies, and benchmarks for success.
限制我们充分利用最新一代治疗性抗体潜力的一个主要挑战是，临床上确定的疾病特异性靶点很少。因此，下一步的主要工作就是扩大这一靶点的范围。最近，免疫疗法（如收养 T 细胞转移、免疫检查点抑制和嵌合抗原受体（CAR）T 细胞疗法）在临床上取得了成功，这有力地支持了将重点放在人类白细胞抗原（pHLA）呈现的肽的免疫肽组上，这些肽通常由 T 细胞受体（TCR）监测。针对 pHLA 靶点的新型抗体开发催生了类 TCR 抗体，它们作为双特异性 T 细胞参与抗体和 CAR-T 细胞疗法的 CAR，于 2020 年进入临床。在这篇综述中，我们将重点介绍 TCR 类抗体的最新进展，包括治疗模式、工程策略和成功基准。
{"title":"Engineering T-cell receptor–like antibodies for biologics and cell therapy","authors":"Lene S Høydahl , Gøril Berntzen, Geir Å Løset","doi":"10.1016/j.copbio.2024.103224","DOIUrl":"10.1016/j.copbio.2024.103224","url":null,"abstract":"<div><div>A major prevailing challenge limiting our ability to fully harness the potential of the latest-generation therapeutic antibodies is the scarcity of clinically established disease-specific targets. A major next step forward will therefore be to expand this target space. The recent clinical success of immunotherapies such as adoptive T-cell transfer, immune checkpoint inhibition, and chimeric antigen receptor (CAR) T-cell therapy strongly supports focusing on the immunopeptidome of peptides presented by human leukocyte antigen (pHLA) that are normally surveilled by T-cell receptors (TCRs). Directing novel antibody development toward pHLA targets has given rise to TCR-like antibodies, which reached the clinic in 2020, as both bispecific T-cell engaging antibodies and the CARs of CAR-T cell therapies. In this review, we highlight recent advances in TCR-like antibodies, including therapeutic modalities, engineering strategies, and benchmarks for success.</div></div>","PeriodicalId":10833,"journal":{"name":"Current opinion in biotechnology","volume":"90 ","pages":"Article 103224"},"PeriodicalIF":7.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-31DOI: 10.1016/j.copbio.2024.103218
Sara Linciano , Emilia Vigolo , Antonio Rosato , Yoichi Kumada , Alessandro Angelini
Small immunomodulatory payloads (IMMs) such as peptide vaccines and cytokines have the capability to activate and boost the immune response against cancer. However, their clinical use has often been hindered by their poor stability and short circulating half-lives. To enhance the pharmacokinetic properties of small IMMs and promote their trafficking and accumulation in lymphatic and tumor tissues, a large variety of strategies have been developed. One of the most successful relies on the use of serum albumin (SA), the most abundant protein in the circulatory and lymphatic system. Here, we report a comparative analysis of the different covalent and noncovalent SA-based strategies applied so far to improve the efficacy of small IMMs in cancer therapy.
肽疫苗和细胞因子等小型免疫调节有效载荷（IMMs）具有激活和增强抗癌免疫反应的能力。然而，它们的稳定性差、循环半衰期短，往往阻碍了它们的临床应用。为了提高小型 IMMs 的药代动力学特性，促进它们在淋巴和肿瘤组织中的运输和积累，人们开发了多种策略。最成功的策略之一是使用血清白蛋白（SA），它是循环和淋巴系统中最丰富的蛋白质。在这里，我们报告了迄今为止为提高小型 IMMs 在癌症治疗中的疗效而应用的基于共价和非共价 SA 的不同策略的比较分析。
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