Antibodies最新文献

{"title":"A Recombinant Antibody Against Human DRP1 Serine 616 Phosphorylation Enables Detection of BRAF^V600E-Associated Mitochondrial Division in Cancer.","authors":"Shanon T Nizard, Yiyang Chen, Madhavika N Serasinghe, Ruben Fernandez-Rodriguez, Kamrin D Shultz, Jesminara Khatun, Anthony Mendoza, Jesse D Gelles, Juan F Henao-Martinez, Ioana Abraham-Enachescu, Md Abdullah Al Noman, Stella G Bayiokos, J Andrew Duty, Shane Meehan, Mihaela Skobe, Jerry Edward Chipuk","doi":"10.3390/antib15020038","DOIUrl":"10.3390/antib15020038","url":null,"abstract":"<p><strong>Background/objectives: </strong>Mitochondria are dynamic organelles that continuously undergo balanced cycles of fusion and division to maintain optimal function. Mitochondrial division is mediated by Dynamin-Related Protein 1 (DRP1), a cytosolic large GTPase whose phosphorylation at serine 616 (DRP1-S616Ⓟ) promotes its translocation to the outer mitochondrial membrane and organelle division. Dysregulated mitochondrial division disrupts cellular homeostasis and contributes to disease pathogenesis, including cancer. Our prior work demonstrated that the oncogene-induced mitogen-activated protein kinase (MAPK) pathway constitutively phosphorylates DRP1 at serine 616, which is essential to cellular transformation and correlates with oncogene status in patient tissues. Similarly, DRP1-S616Ⓟ is subject to pharmacologic control by targeted therapies against oncogenic MAPK signaling.</p><p><strong>Methods: </strong>Building upon this foundation, we developed and characterized a recombinant murine monoclonal antibody (referred to as 3G11) with high specificity for human DRP1-S616Ⓟ, raised against a peptide derived from the human DRP1 sequence.</p><p><strong>Results: </strong>Using diverse experimental platforms, we demonstrate the robust utility of 3G11 to detect DRP1-S616Ⓟ in melanoma cell extracts and isolated organelles. Immunofluorescence revealed that pharmacologic inhibition of oncogenic MAPK signaling reduces DRP1-S616Ⓟ levels, which correlates with mitochondrial hyperfusion, while immunohistochemistry showed that elevated DRP1-S616Ⓟ expression in human tissues correlates with BRAF^V600E disease.</p><p><strong>Conclusions: </strong>3G11 is a new recombinant antibody for detecting DRP1-S616Ⓟ and supports studies of mitochondrial division in cancer. Together, these findings establish 3G11 as a specific, versatile, renewable, and cost-effective tool for studying mitochondrial division, with strong potential for clinical applications.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760361","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":"Brain Delivery of Antibody-Derived Biologicals for Alzheimer's Disease: An Updated Narrative Review.","authors":"Rachita K Sumbria, Ruben J Boado","doi":"10.3390/antib15020037","DOIUrl":"https://doi.org/10.3390/antib15020037","url":null,"abstract":"<p><p>Antibodies directed against β-amyloid (Aβ) have been developed for the treatment of Alzheimer's disease (AD). However, the in vivo central efficacy is reduced by the poor penetration of antibodies across the blood-brain barrier (BBB). In addition, these antibodies have been associated with adverse effects like amyloid-related imaging abnormalities. Thus, the development of new antibody-based therapies for AD with improved transport across the BBB may improve efficacy and reduce adverse effects. Antibodies targeting the BBB transferrin receptor (TfR) are able to cross the BBB through receptor-mediated transcytosis, producing a global distribution throughout the brain. Along the same line, bispecific antibodies directed to both the BBB TfR and Aβ showed enhanced brain uptake and pharmacological effects with diminished adverse side effects in experimental animal models of AD and in clinical trials. A generation of brain-penetrating fusion proteins targeting the BBB-TfR has been shown to represent novel treatments for AD, and this includes erythropoietin, tumor necrosis factor alpha inhibitors, neprilysin, somatostatin, oligonucleotides, and an antibody activating TREM2. The aim of this article is to review the progress made in the delivery of antibody-derived biologicals to the brain for AD, targeting the BBB-TfR.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760450","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":"Post-Chemotherapy Antibody-Based Continuation and Maintenance Strategies in HER2-Positive Metastatic Breast Cancer: A Translational Narrative Review.","authors":"Katarzyna Pogoda, Karolina Lewińska, Paulina Kalman, Anna Bałata, Piotr J Wysocki","doi":"10.3390/antib15020036","DOIUrl":"https://doi.org/10.3390/antib15020036","url":null,"abstract":"<p><p>The treatment paradigm for HER2-positive metastatic breast cancer has evolved from continuous chemotherapy-based regimens to a model of finite chemotherapy induction followed by sustained antibody-driven disease control. The CLEOPATRA trial established dual HER2 blockade with trastuzumab and pertuzumab plus a taxane as the biological and clinical anchor of this approach, demonstrating that chemotherapy is administered for a defined induction period, after which antibody maintains disease suppression. An increasing body of clinical evidence indicates that antibody-based regimens can be combined with targeted agents, including CDK4/6 inhibitors or HER2 tyrosine kinase inhibitors, to achieve durable disease control without the need for continuous chemotherapy. In the PATINA trial, the addition of palbociclib to trastuzumab, pertuzumab, and endocrine therapy was associated with a clinically meaningful improvement in progression-free survival in hormone receptor-positive, HER2-positive metastatic breast cancer. At the same time, quality of life was maintained despite higher rates of hematologic toxicity. More recently, HER2-CLIMB-05 demonstrated that the addition of tucatinib to dual HER2 antibody therapy significantly prolonged progression-free survival, supporting a model of sustained, multi-agent HER2 pathway suppression. The monarcHER trial provided biological proof of concept that antibody plus CDK4/6 inhibition can achieve disease control without chemotherapy in hormone receptor-positive, HER2-positive disease. Collectively, these advances support a translational framework in which antibody therapy serves as a central component of treatment strategies, with targeted partners selected according to tumor biology and prior therapy. This review summarizes the biological basis, clinical evidence, and future perspectives of antibody-driven maintenance in HER2-positive metastatic breast cancer.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760380","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":"IMGT^® Nomenclature of Immunoglobulins (IG) or Antibodies and T Cell Receptors (TR): A Common Language for Immunoinformatics and Artificial Intelligence (AI).","authors":"Marie-Paule Lefranc, Gérard Lefranc","doi":"10.3390/antib15020035","DOIUrl":"https://doi.org/10.3390/antib15020035","url":null,"abstract":"<p><p>The immunoglobulins (IG) or antibodies and the T cell receptors (TR) are the antigen receptors of the adaptive immune responses (AIR) of jawed vertebrates (<i>Gnathostomata</i>). IMGT^®, the international ImMunoGeneTics information system^®, was created in 1989 by Marie-Paule Lefranc (Laboratoire d'ImmunoGénétique Moléculaire (LIGM), Université de Montpellier and CNRS) to deal with and to manage the huge diversity of IG or antibodies and TR. The founding of IMGT^® marked the advent of immunoinformatics, a new science which emerged at the interface between immunogenetics and bioinformatics. For the first time, the IG and TR variable (V), diversity (D), joining (J) and constant (C) genes were officially recognized as 'genes', as were the conventional genes. The IMGT-ONTOLOGY CLASSIFICATION axiom and the concepts of classification have generated the IMGT nomenclature and the IMGT Scientific chart rules for assigning IMGT names to IG and TR genes and alleles of <i>Homo sapiens</i> and of any other jawed vertebrate species. The IMGT nomenclature is used for genes in locus, in sequences (genomic or rearranged, expressed or not) and in structures enabling comparative immunology, evolutionary immunogenetics, standardized analysis and comparison of IG and TR repertoires analysis in normal or pathologic situations. IMGT nomenclature is used in basic, veterinary, and medical research, in clinical applications (mutation analysis in leukemia and lymphoma), and in therapeutic antibody design, engineering and humanization. By providing consistent and high standard biocuration for the description of the IG and TR loci, genes and alleles, and for the analysis of the IG or antibody and TR-expressed rearranged sequences and proteins and structures, the IMGT nomenclature is the common language for immunoinformatics and artificial intelligence (AI).</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760400","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":"Development of a Human IgG1 Monoclonal Antibody Targeting Transferrin Receptor 1 for Antitumor Drug Delivery.","authors":"Tingting Ji, Zhaoyun Zong, Ningyuan Gong, Minghui Yan, Shiyu Chen","doi":"10.3390/antib15020034","DOIUrl":"https://doi.org/10.3390/antib15020034","url":null,"abstract":"<p><p><b>Background</b>: Transferrin receptor protein 1 (TfR1) plays a central role in cellular iron uptake and is frequently overexpressed in malignant tumor cells, rendering it an attractive target for tumor-directed therapy and drug delivery. <b>Methods</b>: A fully human single-chain variable fragment (scFv) antibody targeting TfR1, termed T8scFv, was isolated from a human scFv phage display library through three rounds of stringent biopanning and subsequently reformatted into a full-length IgG1 antibody (T8IgG1). Binding kinetics were characterized using Octet biolayer interferometry (BLI), while cellular binding and internalization were assessed by flow cytometry and immunofluorescence microscopy, respectively. T8IgG1 was further conjugated to DT3C, a recombinant truncated diphtheria toxin fusion protein, to evaluate its internalization-dependent cytotoxicity in vitro. <b>Results</b>: T8scFv exhibited nanomolar affinity for TfR1 (K_D = 214 ± 1 nM), which was substantially enhanced following conversion to the IgG1 format (T8IgG1, K_D = 18.5 ± 0.1 nM). T8IgG1 specifically recognized TfR1 on the surface of tumor cells and underwent efficient TfR1-mediated internalization. The T8IgG1-DT3C complex significantly reduced cell viability and induced apoptosis in K562 cells in vitro. <b>Conclusions</b>: These findings indicate that T8IgG1 is a moderate-affinity, internalizing anti-TfR1 antibody and highlight its potential as a promising candidate for TfR1-based targeted antitumor drug delivery systems.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760374","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":"Non-COVID-19 Vaccinations and the Induction of Autoantibodies in Pemphigus Diseases: A Review of the Speculative Issue and Our Clinical-Laboratory Experience.","authors":"Maksymilian Markwitz, Natalia Welc, Klementyna Kępińska, Monika Bowszyc-Dmochowska, Marian Dmochowski","doi":"10.3390/antib15020033","DOIUrl":"https://doi.org/10.3390/antib15020033","url":null,"abstract":"<p><p><b>Background</b>: Pemphigus diseases are rare autoimmune blistering disorders mediated by pathogenic autoantibodies directed mainly against desmoglein 1 and desmoglein 3. Although most cases are considered idiopathic, external triggers that can disrupt immune tolerance have been described. Vaccination has been discussed as a potential precipitating factor in autoimmune skin diseases. However, the relationship between vaccination and the induction of pemphigus-related autoantibodies has not been comprehensively summarized. <b>Methods</b>: We conducted a narrative review of all available studies published in the last 25 years identified through medical databases, excluding studies on COVID-19 vaccinations. Reports describing either new-onset pemphigus or exacerbation of preexisting pemphigus with a temporal association to vaccination were included. Clinical characteristics, vaccine type, latency period, direct immunofluorescence findings, and ELISA results for desmoglein autoantibodies were analyzed. In addition, we present our own clinical-laboratory experience illustrating this issue. <b>Results</b>: The current evidence consists predominantly of case reports and small case series. Published cases describe pemphigus vulgaris and pemphigus foliaceus occurring after vaccinations against influenza, hepatitis B, tetanus, diphtheria, pertussis, rabies, and other routinely administered immunizations. The latency period most often ranged from several days to a few weeks. Immunopathological findings were consistent with classical pemphigus diseases, including intercellular IgG deposits in the epidermis and circulating autoantibodies against desmoglein 1 and/or desmoglein 3. Our patient was a 78-year-old woman who developed cutaneous form of pemphigus vulgaris, diagnosed with direct immunofluorescence (DIF) and multiplex ELISA, 10 days after diphtheria-tetanus-pertussis vaccination. The patient had a positive family history of autoimmune blistering disease, namely mucous membrane pemphigoid. <b>Conclusions</b>: Based on the currently available evidence, a direct causal relationship between vaccination and pemphigus diseases cannot be established. Nevertheless, accumulated clinical and serological observations suggest that vaccination may act as a triggering factor in genetically or immunologically predisposed individuals, possibly by amplifying pre-existing subclinical autoreactive immune responses. Further population-based and mechanistic studies are required to clarify this association, while the overall benefits of vaccination remain substantial.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760412","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":"Monoclonal Antibodies in Pregnancy of Patients with Systemic Lupus Erythematosus: Friend or Foe? A Case Report of a Patient with Multiple Pregnancies.","authors":"Chiara Orlandi, Angela Tincani, Micaela Fredi, Laura Andreoli, Francesca Crisafulli, Liala Moschetti, Cecilia Nalli, Maria Grazia Lazzaroni, Marco Taglietti, Matteo Filippini, Sonia Zatti, Laura Picciau, Franco Franceschini, Ilaria Cavazzana","doi":"10.3390/antib15020032","DOIUrl":"https://doi.org/10.3390/antib15020032","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women of childbearing age, and active disease during pregnancy is associated with increased maternal and fetal morbidity. Belimumab is an effective biologic therapy for active SLE; however, its use during pregnancy has long been limited by the scarcity of safety data. Recent evidence and updated international recommendations suggest that belimumab may be considered in selected cases when required to maintain maternal disease control. We report the case of a woman with SLE who experienced three consecutive pregnancies with live births between 2019 and 2024 while receiving belimumab, allowing an intra-individual comparison of different exposure strategies. During the first pregnancy, belimumab was discontinued at conception and was followed by a disease flare in late pregnancy and postpartum. In the second and third pregnancies, belimumab was continued until gestational week 20 following shared decision-making with the patient; nevertheless, disease flares occurred during the third trimester of both pregnancies. All pregnancies resulted in live births at term, with no congenital anomalies, placental insufficiency, or fetal growth restriction. One neonate from the third pregnancy developed early-onset neonatal sepsis and meningitis, which resolved completely after antibiotic treatment. All children are currently growing and developing normally. This case supports a risk-adapted approach to belimumab use during pregnancy. In selected women with SLE at high risk of disease reactivation, continuation of belimumab until mid-gestation may contribute to improved maternal disease control without evident adverse fetal outcomes.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13112972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760358","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":"The Possible Role of Antibodies in Alopecia: A Narrative Review.","authors":"Julia Cieślawska, Mariola Pawlaczyk, Justyna Gornowicz-Porowska","doi":"10.3390/antib15020031","DOIUrl":"https://doi.org/10.3390/antib15020031","url":null,"abstract":"<p><p>Human hair performs a number of important physiological and esthetic functions. Hair loss and alopecia are complex disorders which affect people all over the world. Hair loss can be an early manifestation of various autoimmunological disorders. Despite a growing interest of researchers in the role of immune factors-especially autoantibodies-in the etiology of certain types of alopecia, their role in alopecia remains uncertain. Several potential autoantigens of follicular components, mainly derived from keratinocytes and melanocytes of the hair follicles, have been found to play a role in the development of alopecia areata. The list of autoantigens includes trichohyalin, keratin 16, fibroblast growth factor receptor 3, glycoprotein-100, melanoma-associated antigen recognized by T cells 1, dopachrome tautomerase/tyrosinase-related protein 2, tyrosinase, and tyrosine hydroxylase. This narrative review presents different aspects of immunopathogenesis of alopecia, from physiology (hair follicle immune privilege) to pathology (disruption of hair follicle immune privilege) and signaling pathways. Identification of key autoantigens could potentially pave the way for the development of new, effective, and more targeted immunotherapies for alopecia.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760405","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":"SARS-CoV-2 Infection and COVID-19 Vaccine Antibody Responses in Two Canadian Cohorts of Persons Living with HIV.","authors":"Sharon L Walmsley, Leif Erik Lovblom, Bryan Boyachuk, Curtis Cooper, Valérie Martel-Laferrière, Mona Loutfy, Marie-Louise Vachon, Shariq Haider, Pamela Aldebes, Karen Colwill, Anne Claude Gingras, Freda Qi, Marina B Klein","doi":"10.3390/antib15020030","DOIUrl":"https://doi.org/10.3390/antib15020030","url":null,"abstract":"<p><p><b>Objectives:</b> To determine the incidence and outcomes of SARS-CoV-2 infection and to evaluate seroconversion rates and quantify antibody responses to COVID-19 vaccines in two cohorts of persons living with HIV at a possible higher risk of poor outcomes (HCV coinfection and those over the age of 65 years). <b>Methods:</b> We included participants from two established cohorts of persons living with HIV, those who were older than 65 years of age, and those with hepatitis C (HCV) co-infection. Four hundred and seventy-one participants completed questionnaires on SARS-CoV-2 infection and COVID-19 vaccine doses and submitted peripheral blood specimens for measuring antibody levels to COVID-19 antigens, full-length spike trimer, its receptor binding domain (RBD), and nucleocapsid protein (N) at 6-month intervals up to three visits between February 2021 and December 2024. Logistic and ordinal logistic regression models evaluated predictors of seroconversion and antibody levels. <b>Results:</b> Overall, 51% of participants developed a SARS-CoV-2 infection, but it was mild, with only nine requiring hospital admission and no deaths. Overall, 99% of tested specimens had antibodies above threshold to either spike or RBD proteins. Specimens that did not and those with lower antibody levels had testing earlier in the pandemic, and were from participants with fewer vaccine doses, and did not have natural infection. Age, depression, comorbidity, HCV co-infection, current substance use, CD4 count, or HIV viral load were predictive of antibody level. Those with hybrid immunity had higher antibody responses. <b>Conclusions:</b> In cohorts of persons with HIV-HCV coinfection and those who are ageing, we observed high rates of seroconversion to COVID-19 antigens. Antibody levels were higher among those with more vaccine doses, hybrid immunity, and later in the pandemic waves. Although 51% developed a breakthrough infection, outcomes were mild with no deaths.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760377","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":"Development of Bispecific Antibody Targeting Human IL-17A and IL-6.","authors":"Beata Pamuła, Martyna Banach, Marta Mikońska, Karolina Korytkowska, Krzysztof Lacek, Oliwia Śniadała, Małgorzata Marczak, Krzysztof Flis, Aleksandra Sowińska, Damian Kołakowski, Jerzy Pieczykolan, Beata Zygmunt, Maciej Wieczorek, Olga Abramczyk","doi":"10.3390/antib15020029","DOIUrl":"https://doi.org/10.3390/antib15020029","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Antibodies are a rapidly expanding field in drug discovery, but their monospecificity limits therapeutic applications, particularly in complex inflammatory diseases. Multispecific therapeutics, which combine variable regions targeting two or more antigens, offer potential advantages such as enhanced efficacy, broader target modulation, and reduced side effects. This study aimed to identify and characterize bispecific, VHH-based antibodies simultaneously targeting IL-6 and IL-17A-two key cytokines involved in autoimmune and chronic inflammatory conditions. <b>Methods</b>: A phage display screening was conducted using llama-derived VHH libraries to select binders against human IL-6 and IL-17A. Binding affinities of individual VHHs and assembled bispecific constructs were assessed using Bio-Layer Interferometry (BLI). Functional activity was evaluated using reporter cell lines responsive to IL-6 and IL-17A signaling. Biophysical and quality assessments of selected VHHs and bispecific antibodies were performed using the Uncle screening platform and LabChip capillary electrophoresis. <b>Results</b>: Several high-affinity VHH binders were identified for both IL-6 and IL-17A, and incorporated into bispecific antibody formats. The bispecific candidates exhibited simultaneous inhibition of both cytokine pathways in functional reporter assays. Biophysical characterization confirmed good stability and purity profiles for selected molecules. <b>Conclusions</b>: This study demonstrates the feasibility of generating stable, functional bispecific VHH-based antibodies targeting IL-6 and IL-17A. These constructs show potential as therapeutic agents for treating autoimmune and chronic inflammatory diseases by modulating multiple signaling pathways simultaneously.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760355","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}