Antibodies最新文献_第8页

Episomal Vectors for Stable Production of Recombinant Proteins and Engineered Antibodies. 用于稳定生产重组蛋白质和工程抗体的外显子载体。

IF 4.7

Antibodies Pub Date : 2024-03-11 DOI: 10.3390/antib13010018

Ian Fallahee, Daniel Hawiger

{"title":"Episomal Vectors for Stable Production of Recombinant Proteins and Engineered Antibodies.","authors":"Ian Fallahee, Daniel Hawiger","doi":"10.3390/antib13010018","DOIUrl":"10.3390/antib13010018","url":null,"abstract":"There is tremendous interest in the production of recombinant proteins, particularly bispecific antibodies and antibody-drug conjugates for research and therapeutic use. Here, we demonstrate a highly versatile plasmid system that allows the rapid generation of stable Expi293 cell pools by episomal retention of transfected DNA. By linking protein expression to puromycin resistance through an attenuated internal ribosome entry site, we achieve stable cell pools producing proteins of interest. In addition, split intein-split puromycin-mediated selection of two separate protein expression cassettes allows the stable production of bispecific antibody-like molecules or antibodies with distinct C-terminal heavy chain modifications, such as an antigen on one chain and a sortase tag on the other chain. We also use this novel expression system to generate stable Expi293 cell pools that secrete sortase A Δ59 variant Srt4M. Using these reagents, we prepared a site-specific drug-to-antibody ratio of 1 antibody-siRNA conjugate. We anticipate the simple, robust, and rapid stable protein expression systems described here being useful for a wide variety of applications.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10967652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140292583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Performance Characteristics and Limitations of the Available Assays for the Detection and Quantitation of Monoclonal Free Light Chains and New Emerging Methodologies 用于检测和定量单克隆游离轻链的现有检测方法的性能特点和局限性以及新出现的方法

IF 4.7

Antibodies Pub Date : 2024-03-11 DOI: 10.3390/antib13010019

H. V. Giles, Kamaraj Karunanithi

{"title":"Performance Characteristics and Limitations of the Available Assays for the Detection and Quantitation of Monoclonal Free Light Chains and New Emerging Methodologies","authors":"H. V. Giles, Kamaraj Karunanithi","doi":"10.3390/antib13010019","DOIUrl":"https://doi.org/10.3390/antib13010019","url":null,"abstract":"Light chain measurements form an essential component of the testing strategy for the detection and monitoring of patients with suspected and/or proven plasma cell disorders. Urine-based electrophoretic assays remain at the centre of the international guidelines for response assessment but the supplementary role of serum-free light chain (FLC) assays in response assessment and the detection of disease progression due to their increased sensitivity has been increasingly recognised since their introduction in 2001. Serum FLC assays have also been shown to be prognostic across the spectrum of plasma cell disorders and are now incorporated into risk stratification scores for patients with monoclonal gammopathy of undetermined significance (MGUS), smouldering multiple myeloma, and light chain amyloidosis (AL amyloidosis), as well as being incorporated into the criteria for defining symptomatic multiple myeloma. There are now multiple different commercially available serum FLC assays available with differing performance characteristics, which are discussed in this review, along with the implications of these for patient monitoring. Finally, newer methodologies for the identification and characterisation of monoclonal FLC, including modifications to electrophoretic techniques, mass spectrometry-based assays and Amylite, are also described along with the relevant published data available regarding the performance of each assay.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140253440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Platform-Specific Fc N-Glycan Profiles of an Antisperm Antibody 抗精子抗体的平台特异性 Fc N-糖谱分析

IF 4.7

Antibodies Pub Date : 2024-03-06 DOI: 10.3390/antib13010017

Ellena Nador, Chaoshuang Xia, Philip J. Santangelo, Kevin J. Whaley, Catherine E. Costello, Deborah J. Anderson

{"title":"Platform-Specific Fc N-Glycan Profiles of an Antisperm Antibody","authors":"Ellena Nador, Chaoshuang Xia, Philip J. Santangelo, Kevin J. Whaley, Catherine E. Costello, Deborah J. Anderson","doi":"10.3390/antib13010017","DOIUrl":"https://doi.org/10.3390/antib13010017","url":null,"abstract":"IgG Fc N-glycosylation is necessary for effector functions and is an important component of quality control. The choice of antibody manufacturing platform has the potential to significantly influence the Fc glycans of an antibody and consequently alter their activity and clinical profile. The Human Contraception Antibody (HCA) is an IgG1 antisperm monoclonal antibody (mAb) currently in clinical development as a novel, non-hormonal contraceptive. Part of its development is selecting a suitable expression platform to manufacture HCA for use in the female reproductive tract. Here, we compared the Fc glycosylation of HCA produced in two novel mAb manufacturing platforms, namely transgenic tobacco plants (Nicotiana benthamiana; HCA-N) and mRNA-mediated expression in human vaginal cells (HCAmRNA). The Fc N-glycan profiles of the two HCA products were determined using mass spectrometry. Major differences in site occupancy, glycan types, and glycoform distributions were revealed. To address how these differences affect Fc function, antibody-dependent cellular phagocytosis (ADCP) assays were performed. The level of sperm phagocytosis was significantly lower in the presence of HCA-N than HCAmRNA. This study provides evidence that the two HCA manufacturing platforms produce functionally distinct HCAs; this information could be useful for the selection of an optimal platform for HCA clinical development and for mAbs in general.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140261783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunogenicity and Loss of Effectiveness of Biologic Therapy for Inflammatory Bowel Disease Patients Due to Anti-Drug Antibody Development. 炎症性肠病患者生物疗法的免疫原性和抗药性抗体发展导致的疗效丧失。

IF 4.7

Antibodies Pub Date : 2024-02-26 DOI: 10.3390/antib13010016

Tsvetelina Velikova, Metodija Sekulovski, Monika Peshevska-Sekulovska

{"title":"Immunogenicity and Loss of Effectiveness of Biologic Therapy for Inflammatory Bowel Disease Patients Due to Anti-Drug Antibody Development.","authors":"Tsvetelina Velikova, Metodija Sekulovski, Monika Peshevska-Sekulovska","doi":"10.3390/antib13010016","DOIUrl":"10.3390/antib13010016","url":null,"abstract":"Many patients with inflammatory bowel disease (IBD) experience a loss of effectiveness to biologic therapy (i.e., anti-TNF therapy, etc.). Therefore, in addition to the adverse effects of the treatment, these patients also face failure to achieve and maintain remission. Immunogenicity, the process of production of antibodies to biological agents, is fundamental to the evolution of loss of response to treatment in IBD patients. The presence of these antibodies in patients is linked to decreased serum drug levels and inhibited biological activity. However, immunogenicity rates exhibit significant variability across inflammatory disease states, immunoassay formats, and time periods. In this review, we aimed to elucidate the immunogenicity and immune mechanisms of antibody formation to biologics, the loss of therapy response, clinical results of biological treatment for IBD from systematic reviews and meta-analyses, as well as to summarize the most recent strategies for overcoming immunogenicity and approaches for managing treatment failure in IBD.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10967499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140292584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a Bispecific IgG1 Antibody Targeting BCMA and PDL1. 开发靶向 BCMA 和 PDL1 的双特异性 IgG1 抗体

IF 4.7

Antibodies Pub Date : 2024-02-20 DOI: 10.3390/antib13010015

Irene Cattaneo, Sylvie Choblet, Rut Valgardsdottir, Muriel Roth, Annamaria Massafra, Marten Beeg, Marco Gobbi, Martine Duonor-Cerutti, Josée Golay

{"title":"Development of a Bispecific IgG1 Antibody Targeting BCMA and PDL1.","authors":"Irene Cattaneo, Sylvie Choblet, Rut Valgardsdottir, Muriel Roth, Annamaria Massafra, Marten Beeg, Marco Gobbi, Martine Duonor-Cerutti, Josée Golay","doi":"10.3390/antib13010015","DOIUrl":"10.3390/antib13010015","url":null,"abstract":"We designed, produced, and purified a novel IgG1-like, bispecific antibody (bsAb) directed against B-cell maturation antigen (BCMA), expressed by multiple myeloma (MM) cells, and an immune checkpoint inhibitor (ICI), PDL1, expressed in the MM microenvironment. The BCMA×PDL1 bsAb was fully characterized in vitro. BCMA×PDL1 bound specifically and simultaneously, with nM affinity, to both native membrane-bound antigens and to the recombinant soluble antigen fragments, as shown by immunophenotyping analyses and surface plasmon resonance (SPR), respectively. The binding affinity of bsAb for PDL1 and BCMA was similar to each other, but PDL1 affinity was about 10-fold lower in the bsAb compared to parent mAb, probably due to the steric hindrance associated with the more internal anti-PDL1 Fab. The bsAb was also able to functionally block both antigen targets with IC50 in the nM range. The bsAb Fc was functional, inducing human-complement-dependent cytotoxicity as well as ADCC by NK cells in 24 h killing assays. Finally, BCMA×PDL1 was effective in 7-day killing assays with peripheral blood mononuclear cells as effectors, inducing up to 75% of target MM cell line killing at a physiologically attainable, 6 nM, concentration. These data provide the necessary basis for future optimization and in vivo testing of this novel bsAb.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10885062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Engineered Mouse Model That Generates a Diverse Repertoire of Endogenous, High-Affinity Common Light Chain Antibodies 一种能产生多种内源性高亲和力普通轻链抗体的工程小鼠模型

IF 4.7

Antibodies Pub Date : 2024-02-08 DOI: 10.3390/antib13010014

Yinghui Rong, I-Ling Chen, Lance Larrabee, Manali S. Sawant, G. Fuh, Patrick Koenig

{"title":"An Engineered Mouse Model That Generates a Diverse Repertoire of Endogenous, High-Affinity Common Light Chain Antibodies","authors":"Yinghui Rong, I-Ling Chen, Lance Larrabee, Manali S. Sawant, G. Fuh, Patrick Koenig","doi":"10.3390/antib13010014","DOIUrl":"https://doi.org/10.3390/antib13010014","url":null,"abstract":"Bispecific antibodies have gained increasing popularity as therapeutics as they enable novel activities that cannot be achieved with monospecific antibodies. Some of the most popular bispecific formats are molecules in which two Fab arms with different antigen specificities are combined into one IgG-like molecule. One way to produce these bispecific molecules requires the discovery of antibodies against the two antigens of interest that share a common light chain. Here, we present the generation and characterization of a common light chain mouse model, in which the endogenous IGKJ cluster is replaced with a prearranged, modified murine IGKV10-96/IGKJ1 segment. We demonstrate that genetic modification does not impact B-cell development. Upon immunization with ovalbumin, the animals generate an antibody repertoire with VH gene segment usage of a similar diversity to wildtype mice, while the light chain diversity is restricted to antibodies derived from the prearranged IGKV10-96/IGKJ1 germline. We further show that the clonotype diversity of the common light chain immune repertoire matches the diversity of immune repertoire isolated from wildtype mice. Finally, the common light chain anti-ovalbumin antibodies have only slightly lower affinities than antibodies isolated from wildtype mice, demonstrating the suitability of these animals for antibody discovery for bispecific antibody generation.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139793193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SARS-CoV-2: A Glance at the Innate Immune Response Elicited by Infection and Vaccination SARS-CoV-2：感染和疫苗接种引起的先天性免疫反应一瞥

IF 4.7

Antibodies Pub Date : 2024-02-08 DOI: 10.3390/antib13010013

N. Manfrini, Samuele Notarbartolo, Renata Grifantini, E. Pesce

引用次数: 0

An Engineered Mouse Model That Generates a Diverse Repertoire of Endogenous, High-Affinity Common Light Chain Antibodies 一种能产生多种内源性高亲和力普通轻链抗体的工程小鼠模型

IF 4.7

Antibodies Pub Date : 2024-02-08 DOI: 10.3390/antib13010014

Yinghui Rong, I-Ling Chen, Lance Larrabee, Manali S. Sawant, G. Fuh, Patrick Koenig

{"title":"An Engineered Mouse Model That Generates a Diverse Repertoire of Endogenous, High-Affinity Common Light Chain Antibodies","authors":"Yinghui Rong, I-Ling Chen, Lance Larrabee, Manali S. Sawant, G. Fuh, Patrick Koenig","doi":"10.3390/antib13010014","DOIUrl":"https://doi.org/10.3390/antib13010014","url":null,"abstract":"Bispecific antibodies have gained increasing popularity as therapeutics as they enable novel activities that cannot be achieved with monospecific antibodies. Some of the most popular bispecific formats are molecules in which two Fab arms with different antigen specificities are combined into one IgG-like molecule. One way to produce these bispecific molecules requires the discovery of antibodies against the two antigens of interest that share a common light chain. Here, we present the generation and characterization of a common light chain mouse model, in which the endogenous IGKJ cluster is replaced with a prearranged, modified murine IGKV10-96/IGKJ1 segment. We demonstrate that genetic modification does not impact B-cell development. Upon immunization with ovalbumin, the animals generate an antibody repertoire with VH gene segment usage of a similar diversity to wildtype mice, while the light chain diversity is restricted to antibodies derived from the prearranged IGKV10-96/IGKJ1 germline. We further show that the clonotype diversity of the common light chain immune repertoire matches the diversity of immune repertoire isolated from wildtype mice. Finally, the common light chain anti-ovalbumin antibodies have only slightly lower affinities than antibodies isolated from wildtype mice, demonstrating the suitability of these animals for antibody discovery for bispecific antibody generation.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139853103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SARS-CoV-2: A Glance at the Innate Immune Response Elicited by Infection and Vaccination SARS-CoV-2：感染和疫苗接种引起的先天性免疫反应一瞥

IF 4.7

Antibodies Pub Date : 2024-02-08 DOI: 10.3390/antib13010013

N. Manfrini, Samuele Notarbartolo, Renata Grifantini, E. Pesce

引用次数: 0

Immune-Mediated Necrotizing Myopathy (IMNM): A Story of Antibodies 免疫相关坏死性肌病 (IMNM)：抗体的故事

IF 4.7

Antibodies Pub Date : 2024-02-07 DOI: 10.3390/antib13010012

Sarah Julien, Inès Challier, Marine Malleter, F. Jouen, L. Drouot, Olivier Boyer

引用次数: 0