Antibodies最新文献

{"title":"Rapid Generation of Murine Bispecific Antibodies Using FAST-IgTM for Preclinical Screening of HER2/CD3 T-Cell Engagers","authors":"Hikaru Koga, H. Kuroi, Rena Hirano, Hiroyuki Hirayama, Yoshiaki Nabuchi, T. Kuramochi","doi":"10.3390/antib13010003","DOIUrl":"https://doi.org/10.3390/antib13010003","url":null,"abstract":"Bispecific antibodies (BsAbs) can bind to two different antigens, enabling therapeutic concepts that cannot be achieved with monoclonal antibodies. Immuno-competent mice are essential for validating drug discovery concepts, necessitating the development of surrogate mouse BsAbs. In this study, we explored the potential of FAST-IgTM, a previously reported BsAb technology, for mouse BsAb production. We investigated charge-based orthogonal Fab mutations to facilitate the correct assembly of heavy and light chains of mouse antibodies and employed knobs-into-holes mutations to facilitate the heterodimerization of heavy chains. We combined five anti-CD3 and two anti-HER2 antibodies in mouse IgG1 and IgG2a subclasses. These 20 BsAbs were analyzed using mass spectrometry or ion exchange chromatography to calculate the percentages of BsAbs with correct chain pairing (BsAb yields). Using FAST-Ig, 19 out of the 20 BsAbs demonstrated BsAb yields of 90% or higher after simple protein A purification from transiently expressed antibodies in Expi293F cells. Importantly, the mouse BsAbs maintained their fundamental physicochemical properties and affinity against each antigen. A Jurkat NFAT-luciferase reporter cell assay demonstrated the combined effects of epitope, affinity, and subclasses. Our findings highlight the potential of FAST-Ig technology for efficiently generating mouse BsAbs for preclinical studies.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139452373","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}

{"title":"A Novel Anti-CD47 Nanobody Tetramer for Cancer Therapy.","authors":"Nataliya M Ratnikova, Yulia Kravchenko, Anna Ivanova, Vladislav Zhuchkov, Elena Frolova, Stepan Chumakov","doi":"10.3390/antib13010002","DOIUrl":"10.3390/antib13010002","url":null,"abstract":"<p><p>CD47 acts as a defense mechanism for tumor cells by sending a \"don't eat me\" signal via its bond with SIRPα. With CD47's overexpression linked to poor cancer outcomes, its pathway has become a target in cancer immunotherapy. Though monoclonal antibodies offer specificity, they have limitations like the large size and production costs. Nanobodies, due to their small size and unique properties, present a promising therapeutic alternative. In our study, a high-affinity anti-CD47 nanobody was engineered from an immunized alpaca. We isolated a specific VHH from the phage library, which has nanomolar affinity to SIRPα, and constructed a streptavidin-based tetramer. The efficacy of the nanobody and its derivative was evaluated using various assays. The new nanobody demonstrated higher affinity than the monoclonal anti-CD47 antibody, B6H12.2. The nanobody and its derivatives also stimulated substantial phagocytosis of tumor cell lines and induced apoptosis in U937 cells, a response confirmed in both in vitro and in vivo settings. Our results underscore the potential of the engineered anti-CD47 nanobody as a promising candidate for cancer immunotherapy. The derived nanobody could offer a more effective, cost-efficient alternative to conventional antibodies in disrupting the CD47-SIRPα axis, opening doors for its standalone or combinatorial therapeutic applications in oncology.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10801496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511584","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}

{"title":"Antiphospholipid Antibodies Associated with Native Arteriovenous Fistula Complications in Hemodialysis Patients: A Comprehensive Review of the Literature","authors":"M. Taghavi, Abla Jabrane, Lucas Jacobs, Maria do Carmo Filomena Mesquita, Anne Demulder, Joëlle Nortier","doi":"10.3390/antib13010001","DOIUrl":"https://doi.org/10.3390/antib13010001","url":null,"abstract":"Antiphospholipid antibody (aPL)-persistent positivity is frequent in hemodialysis (HD) patients. Native arteriovenous fistula (AVF) complications such as stenosis and thrombosis are among the most important causes of morbidity and mortality in hemodialysis patients. The association between aPL positivity and AVF thrombosis seems to now be well established. However, whether aPL positivity is associated with other AVF complications, such as maturation failure or stenosis, is not well known. Given the significant impact of AVF failure on patient’s prognosis, it is of interest to further investigate this particular point in order to improve prevention, surveillance and treatment, and, ultimately, the patient’s outcome. This literature review aims to report the recent literature on aPL-associated native AVF complications.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139391300","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}

{"title":"Heterogeneity in Disulfide Bond Reduction in IgG1 Antibodies Is Governed by Solvent Accessibility of the Cysteines.","authors":"Ramakrishnan Natesan, Andrew B Dykstra, Akash Banerjee, Neeraj J Agrawal","doi":"10.3390/antib12040083","DOIUrl":"10.3390/antib12040083","url":null,"abstract":"<p><p>We studied unpaired cysteine levels and disulfide bond susceptibility in four different γ-immunoglobulin antibodies using liquid chromatography-mass spectrometry. Our choice of differential alkylating agents ensures that the differential peaks are non-overlapping, thus allowing us to accurately quantify free cysteine levels. For each cysteine residue, we observed no more than 5% to be unpaired, and the free cysteine levels across antibodies were slightly higher in those containing lambda light chains. Interchain and hinge residues were highly susceptible to reducing stresses and showed a 100-1000-fold higher rate of reduction compared to intrachain cysteines. Estimations of the solvent-accessible surface for individual cysteines in IgG1, using an implicit all-atom molecular dynamics simulation, show that interchain and hinge cysteines have >1000-fold higher solvent accessibility compared to intrachain cysteines. Further analyses show that solvent accessibility and the rate of reduction are linearly correlated. Our work clearly establishes the fact that a cysteine's accessibility to the surrounding solvent is one of the primary determinants of its disulfide bond stability.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10741012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138827899","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}

{"title":"Pre-Pandemic Cross-Reactive Immunity against SARS-CoV-2 among Siberian Populations.","authors":"Olga N Shaprova, Daniil V Shanshin, Evgeniia A Kolosova, Sophia S Borisevich, Artem A Soroka, Iuliia A Merkuleva, Artem O Nikitin, Ekaterina A Volosnikova, Nikita D Ushkalenko, Anna V Zaykovskaya, Oleg V Pyankov, Svetlana A Elchaninova, Dmitry N Shcherbakov, Tatiana N Ilyicheva","doi":"10.3390/antib12040082","DOIUrl":"10.3390/antib12040082","url":null,"abstract":"<p><p>In December 2019, a new coronavirus, SARS-CoV-2, was found to in Wuhan, China. Cases of infection were subsequently detected in other countries in a short period of time, resulting in the declaration of the COVID-19 pandemic by the World Health Organization (WHO) on 11 March 2020. Questions about the impact of herd immunity of pre-existing immune reactivity to SARS-CoV-2 on COVID-19 severity, associated with the immunity to seasonal manifestation, are still to be resolved and may be useful for understanding some processes that precede the emergence of a pandemic virus. Perhaps this will contribute to understanding some of the processes that precede the emergence of a pandemic virus. We assessed the specificity and virus-neutralizing capacity of antibodies reacting with the nucleocapsid and spike proteins of SARS-CoV-2 in a set of serum samples collected in October and November 2019, before the first COVID-19 cases were documented in this region. Blood serum samples from 799 residents of several regions of Siberia, Russia, (the Altai Territory, Irkutsk, Kemerovo and Novosibirsk regions, the Republic of Altai, Buryatia, and Khakassia) were analyzed. Sera of non-infected donors were collected within a study of seasonal influenza in the Russian Federation. The sample collection sites were located near the flyways and breeding grounds of wild waterfowl. The performance of enzyme-linked immunosorbent assay (ELISA) for the collected sera included the usage of recombinant SARS-CoV-2 protein antigens: full-length nucleocapsid protein (CoVN), receptor binding domain (RBD) of S-protein and infection fragment of the S protein (S5-6). There were 183 (22.9%) sera reactive to the S5-6, 270 (33.8%) sera corresponding to the full-length N protein and 128 (16.2%) sera simultaneously reactive to both these proteins. Only 5 out of 799 sera had IgG antibodies reactive to the RBD. None of the sera exhibited neutralizing activity against the nCoV/Victoria/1/2020 SARS-CoV-2 strain in Vero E6 cell culture. The data obtained in this study suggest that some of the population of the analyzed regions of Russia had cross-reactive humoral immunity against SARS-CoV-2 before the COVID-19 pandemic started. Moreover, among individuals from relatively isolated regions, there were significantly fewer reliably cross-reactive sera. The possible significance of these data and impact of cross-immunity to SARS-CoV-2 on the prevalence and mortality of COVID-19 needs further assessment.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10741209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138827901","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}

{"title":"Role of Specific Autoantibodies in Neurodegenerative Diseases: Pathogenic Antibodies or Promising Biomarkers for Diagnosis","authors":"Dimitrina Miteva, G. Vasilev, T. Velikova","doi":"10.3390/antib12040081","DOIUrl":"https://doi.org/10.3390/antib12040081","url":null,"abstract":"Neurodegenerative diseases (NDDs) affect millions of people worldwide. They develop due to the pathological accumulation and aggregation of various misfolded proteins, axonal and synaptic loss and dysfunction, inflammation, cytoskeletal abnormalities, defects in DNA and RNA, and neuronal death. This leads to the activation of immune responses and the release of the antibodies against them. Recently, it has become clear that autoantibodies (Aabs) can contribute to demyelination, axonal loss, and brain and cognitive dysfunction. This has significantly changed the understanding of the participation of humoral autoimmunity in neurodegenerative disorders. It is crucial to understand how neuroinflammation is involved in neurodegeneration, to aid in improving the diagnostic and therapeutic value of Aabs in the future. This review aims to provide data on the immune system’s role in NDDs, the pathogenic role of some specific Aabs against molecules associated with the most common NDDs, and their potential role as biomarkers for monitoring and diagnosing NDDs. It is suggested that the autoimmune aspects of NDDs will facilitate early diagnosis and help to elucidate previously unknown aspects of the pathobiology of these diseases.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138588533","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}

{"title":"Neutralization of Different Variants of SARS-CoV-2 by a F(ab')2 Preparation from Sera of Horses Immunized with the Viral Receptor Binding Domain.","authors":"Mariajosé Rodriguez-Nuñez, Mariana Del Valle Cepeda, Carlos Bello, Miguel Angel Lopez, Yoneira Sulbaran, Carmen Luisa Loureiro, Ferdinando Liprandi, Rossana Celeste Jaspe, Flor Helene Pujol, Héctor Rafael Rangel","doi":"10.3390/antib12040080","DOIUrl":"10.3390/antib12040080","url":null,"abstract":"<p><p>The Receptor Binding Domain (RBD) of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, is the functional region of the viral Spike protein (S), which is involved in cell attachment to target cells. The virus has accumulated progressively mutations in its genome, particularly in the RBD region, many of them associated with immune evasion of the host neutralizing antibodies. Some of the viral lineages derived from this evolution have been classified as Variant of Interest (VOI) or Concern (VOC). The neutralizing capacity of a F(ab')2 preparation from sera of horses immunized with viral RBD was evaluated by lytic plaque reduction assay against different SARS-CoV-2 variants. A F(ab')2 preparation of a hyperimmune serum after nine immunizations with RBD exhibited a high titer of neutralizing antibodies against the ancestral-like strain (1/18,528). A reduction in the titer of the F(ab')2 preparation was observed against the different variants tested compared to the neutralizing activity against the ancestral-like strain. The highest reduction in the neutralization titer was observed for the Omicron VOC (4.7-fold), followed by the Mu VOI (2.6), Delta VOC (1.8-fold), and Gamma VOC (1.5). Even if a progressive reduction in the neutralizing antibodies titer against the different variants evaluated was observed, the serum still exhibited a neutralizing titer against the Mu VOI and the Omicron VOC (1/7113 and 1/3918, respectively), the evaluated strains most resistant to neutralization. Therefore, the preparation retained neutralizing activity against all the strains tested.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10740526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138827900","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}

{"title":"Navigating the Challenges of Gluten Enteropathy and Infertility: The Role of Celiac-Related Antibodies and Dietary Changes","authors":"Monika Peshevska-Sekulovska, Milena Gulinac, Radoslav Rangelov, Desislava Docheva, T. Velikova, M. Sekulovski","doi":"10.3390/antib12040079","DOIUrl":"https://doi.org/10.3390/antib12040079","url":null,"abstract":"Celiac disease (CD) is an autoimmune condition that is initiated in genetically susceptible individuals by the exposure of the intestines to gluten, and the early start of symptoms is related to malabsorption. Atypical variants of the illness are often identified in adulthood and are frequently associated with manifestations outside of the intestines, including metabolic osteopathy, anemia, and dermatitis herpetiformis. But also, empirical data suggest a correlation between CD and reproductive abnormalities, including repeated abortions. Infertility and repeated miscarriages frequently manifest in women diagnosed with CD and may serve as the initial clinical indication of a subclinical form. Furthermore, the condition may manifest as amenorrhea, infertility, and the delivery of infants with a low birth weight. Regarding the mechanisms of CD in infertility, along with the anti-tTG action to hinder the invasiveness of trophoblast, these antibodies could damage endometrial angiogenesis, which has been shown in in vitro models with human endometrial cells and in vivo in murine models. Another important aspect is the role of nutrient deficiencies, such as zinc deficiency (connected to impaired hormone production, secondary amenorrhea, and pre-eclampsia) and folic acid, etc. Therefore, our objective was to conduct a comprehensive review of the existing literature pertaining to this specific topic and to elucidate the role of the autoantibodies in its pathogenesis.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138596009","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}

{"title":"Prediction of Antibody Viscosity from Dilute Solution Measurements","authors":"Kamal Bhandari, Yangjie Wei, Brendan R. Amer, Emma M. Pelegri-O’Day, Joon Huh, J. Schmit","doi":"10.3390/antib12040078","DOIUrl":"https://doi.org/10.3390/antib12040078","url":null,"abstract":"The high antibody doses required to achieve a therapeutic effect often necessitate high-concentration products that can lead to challenging viscosity issues in production and delivery. Predicting antibody viscosity in early development can play a pivotal role in reducing late-stage development costs. In recent years, numerous efforts have been made to predict antibody viscosity through dilute solution measurements. A key finding is that the entanglement of long, flexible complexes contributes to the sharp rise in antibody viscosity at the required dosing. This entanglement model establishes a connection between the two-body binding affinity and the many-body viscosity. Exploiting this insight, this study connects dilute solution measurements of self-association to high-concentration viscosity profiles to quantify the relationship between these regimes. The resulting model has exhibited success in predicting viscosity at high concentrations (around 150 mg/mL) from dilute solution measurements, with only a few outliers remaining. Our physics-based approach provides an understanding of fundamental physics, interpretable connections to experimental data, the potential to extrapolate beyond training conditions, and the capacity to effectively explain the physical mechanics behind these outliers. Conducting hypothesis-driven experiments that specifically target the viscosity and relaxation mechanisms of outlier molecules may allow us to unravel the intricacies of their behavior and, in turn, enhance the performance of our model.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138623060","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}

{"title":"Factors Associated with SARS-CoV-2 Infection Evaluated by Antibody Response in a Sample of Workers from the Emilia-Romagna Region, Northern Italy","authors":"S. Paduano, Michele Granata, Sara Turchi, A. Modenese, Pasquale Galante, A. Poggi, I. Marchesi, G. Frezza, Giulia Dervishaj, Roberto Vivoli, Sara Verri, Simona Marchetti, F. Gobba, A. Bargellini","doi":"10.3390/antib12040077","DOIUrl":"https://doi.org/10.3390/antib12040077","url":null,"abstract":"Factors associated with SARS-CoV-2 infection risk are still debated. This case–control study aims to investigate the possible relationship between SARS-CoV-2 infection, evaluated through antibody response, and the main sociodemographic, occupational, clinical-anamnestic, and biochemical factors in a population of Modena province (Northern Italy), mainly workers. Both workers who voluntarily joined the screening campaign proposed by companies and self-referred individuals who underwent serological testing were enrolled. Subjects with antibody positivity were recruited as cases (n = 166) and subjects tested negative (n = 239) as controls. A questionnaire on sociodemographic, occupational, and clinical data was administered through telephone interviews. Serum zinc/iron/copper/chromium/nickel, vitamins D/B12, folates, triglycerides, and LDL/HDL/total cholesterol were measured. Cases lived more often in urban areas (61.8% vs. 57%). Cases and controls did not differ significantly by working macrocategories, but the percentage of workers in the ceramic sector was higher among cases. Low adherence to preventive measures in the workplace was more frequent among seropositives. Folate concentration was significantly lower among cases. Therefore, adequate folate levels, living in rural areas, and good adherence to preventive strategies seem protective against infection. Workers in the ceramic sector seem to be at greater risk; specific factors involved are not defined, but preventive interventions are needed.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138624685","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}