Pub Date : 2024-08-21DOI: 10.1038/s41587-024-02354-5
The therapeutic principle of allogeneic hematopoietic cell transplantation, one the most common forms of cancer immunotherapy, is alloreactivity, yet its molecular determinants remain largely unknown. An analytical framework now enables personalized assessment of alloreactivity from whole-exome sequencing of donor–recipient pairs, to help with prognostication of disease relapse and immune-mediated complications.
{"title":"Framework for predicting alloreactivity in hematopoietic cell transplants","authors":"","doi":"10.1038/s41587-024-02354-5","DOIUrl":"https://doi.org/10.1038/s41587-024-02354-5","url":null,"abstract":"The therapeutic principle of allogeneic hematopoietic cell transplantation, one the most common forms of cancer immunotherapy, is alloreactivity, yet its molecular determinants remain largely unknown. An analytical framework now enables personalized assessment of alloreactivity from whole-exome sequencing of donor–recipient pairs, to help with prognostication of disease relapse and immune-mediated complications.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21DOI: 10.1038/s41587-024-02350-9
We have discovered an effect, termed stacking-induced intermolecular charge transfer-enhanced Raman scattering (SICTERS), that enhances the Raman signal intensities of small molecules by relying on their self-stacking rather than external substrates. This effect enables the design of substrate-free small-molecule probes for high-resolution, non-invasive transdermal Raman imaging of lymphatic drainage and microvessels.
{"title":"Small molecules self-organized in an orderly manner to enhance Raman signals","authors":"","doi":"10.1038/s41587-024-02350-9","DOIUrl":"https://doi.org/10.1038/s41587-024-02350-9","url":null,"abstract":"We have discovered an effect, termed stacking-induced intermolecular charge transfer-enhanced Raman scattering (SICTERS), that enhances the Raman signal intensities of small molecules by relying on their self-stacking rather than external substrates. This effect enables the design of substrate-free small-molecule probes for high-resolution, non-invasive transdermal Raman imaging of lymphatic drainage and microvessels.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raman spectroscopy using surface-enhanced Raman scattering (SERS) nanoprobes represents an ultrasensitive and high-precision technique for in vivo imaging. Clinical translation of SERS nanoprobes has been hampered by biosafety concerns about the metal substrates used to enhance Raman signals. We report a set of small molecules with bis-thienyl-substituted benzobisthiadiazole structures that enhance Raman signal through self-stacking rather than external substrates. In our technique, called stacking-induced charge transfer-enhanced Raman scattering (SICTERS), the self-stacked small molecules form an ordered spatial arrangement that enables three-dimensional charge transfer between neighboring molecules. The Raman scattering cross-section of SICTERS nanoprobes is 1350 times higher than that of conventional SERS gold nanoprobes of similar particle size. SICTERS outperforms SERS in terms of in vivo imaging sensitivity, resolution and depth. SICTERS is capable of noninvasive Raman imaging of blood and lymphatic vasculatures, which has not been achieved by SERS. SICTERS represents an alternative technique to enhance Raman scattering for guiding the design of ultrasensitive substrate-free Raman imaging probes.
{"title":"Self-stacked small molecules for ultrasensitive, substrate-free Raman imaging in vivo","authors":"Shuai Gao, Yongming Zhang, Kai Cui, Sihang Zhang, Yuanyuan Qiu, Yunhui Liao, Haoze Wang, Sheng Yu, Liyang Ma, Hongzhuan Chen, Minbiao Ji, Xiaohong Fang, Wei Lu, Zeyu Xiao","doi":"10.1038/s41587-024-02342-9","DOIUrl":"https://doi.org/10.1038/s41587-024-02342-9","url":null,"abstract":"<p>Raman spectroscopy using surface-enhanced Raman scattering (SERS) nanoprobes represents an ultrasensitive and high-precision technique for in vivo imaging. Clinical translation of SERS nanoprobes has been hampered by biosafety concerns about the metal substrates used to enhance Raman signals. We report a set of small molecules with bis-thienyl-substituted benzobisthiadiazole structures that enhance Raman signal through self-stacking rather than external substrates. In our technique, called stacking-induced charge transfer-enhanced Raman scattering (SICTERS), the self-stacked small molecules form an ordered spatial arrangement that enables three-dimensional charge transfer between neighboring molecules. The Raman scattering cross-section of SICTERS nanoprobes is 1350 times higher than that of conventional SERS gold nanoprobes of similar particle size. SICTERS outperforms SERS in terms of in vivo imaging sensitivity, resolution and depth. SICTERS is capable of noninvasive Raman imaging of blood and lymphatic vasculatures, which has not been achieved by SERS. SICTERS represents an alternative technique to enhance Raman scattering for guiding the design of ultrasensitive substrate-free Raman imaging probes.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-21DOI: 10.1038/s41587-024-02348-3
Nicoletta Cieri, Nidhi Hookeri, Kari Stromhaug, Liang Li, Julia Keating, Paula Díaz-Fernández, Valle Gómez-García de Soria, Jonathan Stevens, Raphael Kfuri-Rubens, Yiren Shao, Kameron A. Kooshesh, Kaila Powell, Helen Ji, Gabrielle M. Hernandez, Jennifer Abelin, Susan Klaeger, Cleo Forman, Karl R. Clauser, Siranush Sarkizova, David A. Braun, Livius Penter, Haesook T. Kim, William J. Lane, Giacomo Oliveira, Leslie S. Kean, Shuqiang Li, Kenneth J. Livak, Steven A. Carr, Derin B. Keskin, Cecilia Muñoz-Calleja, Vincent T. Ho, Jerome Ritz, Robert J. Soiffer, Donna Neuberg, Chip Stewart, Gad Getz, Catherine J. Wu
T cell alloreactivity against minor histocompatibility antigens (mHAgs)—polymorphic peptides resulting from donor–recipient (D–R) disparity at sites of genetic polymorphisms—is at the core of the therapeutic effect of allogeneic hematopoietic cell transplantation (allo-HCT). Despite the crucial role of mHAgs in graft-versus-leukemia (GvL) and graft-versus-host disease (GvHD) reactions, it remains challenging to consistently link patient-specific mHAg repertoires to clinical outcomes. Here we devise an analytic framework to systematically identify mHAgs, including their detection on HLA class I ligandomes and functional verification of their immunogenicity. The method relies on the integration of polymorphism detection by whole-exome sequencing of germline DNA from D–R pairs with organ-specific transcriptional- and proteome-level expression. Application of this pipeline to 220 HLA-matched allo-HCT D–R pairs demonstrated that total and organ-specific mHAg load could independently predict the occurrence of acute GvHD and chronic pulmonary GvHD, respectively, and defined promising GvL targets, confirmed in a validation cohort of 58 D–R pairs, for the prevention or treatment of post-transplant disease recurrence.
T细胞对次要组织相容性抗原（mHAgs）的异体活性--由基因多态性部位的供体-受体（D-R）差异产生的多态肽--是异基因造血细胞移植（allo-HCT）治疗效果的核心。尽管mHAgs在移植物抗白血病（GvL）和移植物抗宿主病（GvHD）反应中起着至关重要的作用，但要将患者特异性的mHAg复合物与临床结果始终联系起来仍具有挑战性。在这里，我们设计了一个分析框架来系统地识别 mHAg，包括在 HLA I 类配体上检测它们，并对它们的免疫原性进行功能验证。该方法依赖于通过对D-R配对的种系DNA进行全外显子测序，将多态性检测与器官特异性转录和蛋白质组水平表达相结合。将该方法应用于220对HLA匹配的异体HCT D-R，结果表明总mHAg负荷和器官特异性mHAg负荷可分别独立预测急性GvHD和慢性肺GvHD的发生，并确定了有希望的GvL目标，在58对D-R的验证队列中得到证实，可用于预防或治疗移植后疾病复发。
{"title":"Systematic identification of minor histocompatibility antigens predicts outcomes of allogeneic hematopoietic cell transplantation","authors":"Nicoletta Cieri, Nidhi Hookeri, Kari Stromhaug, Liang Li, Julia Keating, Paula Díaz-Fernández, Valle Gómez-García de Soria, Jonathan Stevens, Raphael Kfuri-Rubens, Yiren Shao, Kameron A. Kooshesh, Kaila Powell, Helen Ji, Gabrielle M. Hernandez, Jennifer Abelin, Susan Klaeger, Cleo Forman, Karl R. Clauser, Siranush Sarkizova, David A. Braun, Livius Penter, Haesook T. Kim, William J. Lane, Giacomo Oliveira, Leslie S. Kean, Shuqiang Li, Kenneth J. Livak, Steven A. Carr, Derin B. Keskin, Cecilia Muñoz-Calleja, Vincent T. Ho, Jerome Ritz, Robert J. Soiffer, Donna Neuberg, Chip Stewart, Gad Getz, Catherine J. Wu","doi":"10.1038/s41587-024-02348-3","DOIUrl":"https://doi.org/10.1038/s41587-024-02348-3","url":null,"abstract":"<p>T cell alloreactivity against minor histocompatibility antigens (mHAgs)—polymorphic peptides resulting from donor–recipient (D–R) disparity at sites of genetic polymorphisms—is at the core of the therapeutic effect of allogeneic hematopoietic cell transplantation (allo-HCT). Despite the crucial role of mHAgs in graft-versus-leukemia (GvL) and graft-versus-host disease (GvHD) reactions, it remains challenging to consistently link patient-specific mHAg repertoires to clinical outcomes. Here we devise an analytic framework to systematically identify mHAgs, including their detection on HLA class I ligandomes and functional verification of their immunogenicity. The method relies on the integration of polymorphism detection by whole-exome sequencing of germline DNA from D–R pairs with organ-specific transcriptional- and proteome-level expression. Application of this pipeline to 220 HLA-matched allo-HCT D–R pairs demonstrated that total and organ-specific mHAg load could independently predict the occurrence of acute GvHD and chronic pulmonary GvHD, respectively, and defined promising GvL targets, confirmed in a validation cohort of 58 D–R pairs, for the prevention or treatment of post-transplant disease recurrence.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":46.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19DOI: 10.1038/s41587-024-02358-1
Ken Garber
Each year, Nature Biotechnology highlights companies that have received sizeable early-stage funding in the previous year. A rescued chimeric antigen receptor from Cargo Therapeutics for hard-to-treat lymphomas shows promise in patients while a trispecific advances toward human testing.
{"title":"Editor’s pick: Cargo Therapeutics","authors":"Ken Garber","doi":"10.1038/s41587-024-02358-1","DOIUrl":"10.1038/s41587-024-02358-1","url":null,"abstract":"Each year, Nature Biotechnology highlights companies that have received sizeable early-stage funding in the previous year. A rescued chimeric antigen receptor from Cargo Therapeutics for hard-to-treat lymphomas shows promise in patients while a trispecific advances toward human testing.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":33.1,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02358-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-14DOI: 10.1038/s41587-024-02362-5
{"title":"Biotech news from around the world","authors":"","doi":"10.1038/s41587-024-02362-5","DOIUrl":"10.1038/s41587-024-02362-5","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":33.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-14DOI: 10.1038/s41587-024-02349-2
Martin Pera, Andy Greene, Lon Cardon, Gregory W. Carter, Elissa J. Chesler, Gary Churchill, Vivek Kumar, Cathleen Lutz, Steven Munger, Steve Murray, Kristen O’Connell, Laura Reinholdt, Nadia A. Rosenthal
Comparative studies that integrate genetically diverse mouse models and in vitro cell-based assays will accelerate drug discovery for precision medicine.
将不同基因的小鼠模型与体外细胞检测相结合的比较研究将加速精准医学的药物发现。
{"title":"Improving the predictive power of mouse models","authors":"Martin Pera, Andy Greene, Lon Cardon, Gregory W. Carter, Elissa J. Chesler, Gary Churchill, Vivek Kumar, Cathleen Lutz, Steven Munger, Steve Murray, Kristen O’Connell, Laura Reinholdt, Nadia A. Rosenthal","doi":"10.1038/s41587-024-02349-2","DOIUrl":"10.1038/s41587-024-02349-2","url":null,"abstract":"Comparative studies that integrate genetically diverse mouse models and in vitro cell-based assays will accelerate drug discovery for precision medicine.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":33.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-14DOI: 10.1038/s41587-024-02332-x
Andrew W. Torrance, Cesar de la Fuente-Nunez
The resurrection of strings of extinct molecules raises intriguing questions of patentability and bioethical considerations in an emerging area of patent law.
在专利法的一个新兴领域中，一串串已灭绝分子的复活引发了专利性和生物伦理方面的引人入胜的问题。
{"title":"The patentability and bioethics of molecular de-extinction","authors":"Andrew W. Torrance, Cesar de la Fuente-Nunez","doi":"10.1038/s41587-024-02332-x","DOIUrl":"10.1038/s41587-024-02332-x","url":null,"abstract":"The resurrection of strings of extinct molecules raises intriguing questions of patentability and bioethical considerations in an emerging area of patent law.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":null,"pages":null},"PeriodicalIF":33.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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