Antibodies最新文献

{"title":"Beyond the Surface: Antinuclear Antibodies in Rheumatoid Arthritis-Experiences from a Single-Center, Cross-Sectional Observational Study.","authors":"Hanna Cholerzyńska, Gabriela Kot, Łukasz Świątek, Bogna Grygiel-Górniak","doi":"10.3390/antib15040058","DOIUrl":"10.3390/antib15040058","url":null,"abstract":"<p><p><b>Background:</b> Antinuclear antibodies (ANA) can be detected in patients with rheumatoid arthritis (RA) and pose many diagnostic challenges, especially when RA presents an atypical course and requires differentiation from other systemic connective tissue diseases (sCTDs). This study assessed ANA fluorescence patterns and immunoblot profiles, as well as the relationships between ANA titers, antibody expression intensity, and markers of disease activity in patients with RA. <b>Methods</b>: This single-center, cross-sectional, observational study included 81 RA patients (53 ANA-positive) meeting the 2010 ACR/EULAR classification criteria. ANA titers and fluorescence patterns were assessed using indirect immunofluorescence. Anti-extractable nuclear antigen (ENA) autoantibody profiles and expression intensity were assessed using immunoblot analysis. Demographic, clinical, and laboratory data were obtained. Spearman's rank correlation coefficient was used to analyze the relationship between ANA titers and selected variables. Univariate and multivariate logistic regression analyses were performed to identify factors associated with ANA positivity. <b>Results</b>: The cohort consisted primarily of women (86.4%) with moderate disease activity. ANA fluorescence patterns were heterogeneous, with nucleolar and homogeneous patterns most frequently observed. Immunoblot analysis also revealed diverse autoantibody profiles without a clearly dominant specificity. Ro-52, SS-A, and Sm antibodies were detected more frequently, although their prevalence remained relatively low. No statistically significant correlations were found between ANA titers and inflammatory markers, serological parameters, or disease activity indices. <b>Conclusions</b>: RA patients with positive ANA demonstrated marked immunological heterogeneity, without concomitant symptoms of sCTD. A positive result in RA may reflect generalized immune dysregulation rather than a distinct clinical subtype. Further studies with larger cohorts are needed to clarify the clinical significance of ANAs in rheumatoid arthritis.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576296","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":"Potential Mechanisms of Partial/Transient Response or Resistance to Daratumumab Therapy: A Focus on Anti-Daratumumab Antibodies and Urinary Daratumumab Loss.","authors":"Marco Allinovi, Luca Malatesta, Tiziana Biagioli, Elisabetta Antonioli, Federico Perfetto","doi":"10.3390/antib15040057","DOIUrl":"10.3390/antib15040057","url":null,"abstract":"<p><p>Daratumumab, a human IgG1 monoclonal antibody targeting CD38, is widely used in multiple myeloma and AL amyloidosis. Despite its clinical success, many patients fail to achieve durable responses or relapse, underscoring the importance of understanding resistance mechanisms. Drawing on experience from other better-studied monoclonal antibodies, resistance to daratumumab can be categorized into four main mechanisms: (1) reduced CD38 expression on plasma cells; (2) increased expression of complement inhibitory proteins (CD55/CD59), impairing complement-mediated cytotoxicity; (3) reduced drug bioavailability due to urinary loss in non-selective nephrotic syndrome; and (4) the development of neutralizing anti-daratumumab antibodies. Anti-drug antibodies (ADAs) may represent a potential mechanism of treatment failure through effects on pharmacokinetics, efficacy, and safety, even in patients on daratumumab therapy. Seven different trials have tested anti-daratumumab antibodies. Among them, anti-daratumumab antibodies were identified in only 0-2.4% of patients, and only in a small portion of these has it been proven to be neutralizing. Overall, ADAs appear rare, but these findings are likely underestimated due to short follow-up and suboptimal timing of assessment. In conclusion, standardized ADA monitoring, particularly months after treatment interruption or in cases of inadequate response or infusion-related reactions, may improve patient management and therapeutic outcomes.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576332","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":"Phage-Selected Clickable Gln-Donor Peptide for Lys-Selective Fab Labeling Using Engineered Microbial Transglutaminase.","authors":"Eva Agustriana, Koki Murozono, Kosuke Minamihata, Riko Nishioka, Noriho Kamiya","doi":"10.3390/antib15040056","DOIUrl":"10.3390/antib15040056","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The use of cross-linking enzymes for site-selective and efficient antibody modification has attracted considerable attention. Microbial transglutaminase (MTG)-mediated labeling of IgG at Gln295 has emerged as a promising strategy for preparing antibody-drug conjugates (ADCs). By contrast, selective modification of a specific Lys residue on native antibody surfaces using MTG remains challenging because most Lys residues exhibit low intrinsic reactivity. Here, we address this challenge by exploiting enzyme-antibody proximity together with screening for highly reactive Gln-donor substrates from a random peptide library. <b>Methods</b>: Reactive Gln-donor peptide substrates were first identified from a seven-amino-acid phage-displayed peptide library using a reactive Lys-containing peptide as bait. Based on the obtained sequence, an azide-functionalized Gln-donor peptide suitable for click chemistry was designed. <b>Results</b>: The designed substrate enabled efficient Lys65-selective modification of Fab fragments using a fusion of an engineered MTG zymogen and protein G (EzMTG-pG), followed by functionalization through click chemistry to yield fluorescent Fab conjugates. <b>Conclusions</b>: These results provide practical guidelines for substrate design in MTG-mediated site-selective protein modification.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576266","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":"Detection and Identification of Anti-Neutrophil Antibodies in Immune Neutropenia: Integrating Serology, Genotyping and Clinical Interpretation.","authors":"Elyse Moritz, Renato Cerqueira, Juliana Oliveira Martins, José O Bordin","doi":"10.3390/antib15040054","DOIUrl":"10.3390/antib15040054","url":null,"abstract":"<p><p>Immune-mediated neutropenias comprise a heterogeneous group of disorders characterized by antibody-mediated destruction of neutrophils, in which the detection of anti-neutrophil antibodies remains a significant diagnostic challenge. Human neutrophil antigens (HNAs) are key targets in both autoimmune and alloimmune conditions, and their identification requires an integrated laboratory approach combining serological assays, HNA genotyping, and clinical evaluation. However, variability in assay sensitivity, the presence of low-titer or conformationally dependent antibodies, and interference from anti-HLA antibodies may lead to inconclusive or misleading results. This review summarizes the immunological mechanisms underlying anti-HNA antibody-mediated neutropenia and critically evaluates current laboratory methods, including cell-based and bead-based assays. The role of HNA genotyping in supporting antibody identification and improving diagnostic accuracy is also discussed. In addition, we highlight the importance of interpreting serological findings according to antibody specificity and clinical context. An integrated and multidisciplinary diagnostic approach is essential to ensure accurate diagnosis and appropriate clinical management, while emerging technologies may further improve antibody detection in the future.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576276","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":"Aglycosylated Immunoglobulin G1 Fc Stabilized Through Disulfide Bond Addition Exhibits Compositional Homogeneity and Retains Fc γ Receptor IIIa/CD16a Binding.","authors":"Anjali Shenoy, Daniel J Falconer, Adam W Barb","doi":"10.3390/antib15040055","DOIUrl":"10.3390/antib15040055","url":null,"abstract":"<p><strong>Background: </strong>The interaction between human immunoglobulin G (IgG)1 Fc and the Fc gamma receptor (FcγR) IIIa/CD16a elicits protective immune responses. Antibody N-glycosylation stabilizes the FcγR-binding interface and is thus essential for interaction with wildtype IgG1 Fc. Furthermore, the N-glycan introduces substantial compositional and functional heterogeneity, with distinct glycoforms providing different affinities and discrete responses in vivo. Accordingly, various engineering endeavors to improve antibody binding strive to boost the therapeutic efficacy of monoclonal antibodies but do not directly address compositional heterogeneity.</p><p><strong>Objective: </strong>Here, we describe a previously unexplored approach to engineer IgG1 Fc. We eliminated carbohydrate heterogeneity by removing the N-glycan but stabilizing the FcγR-binding interface with disulfide bonds.</p><p><strong>Conclusions: </strong>These newly generated Fc domains served as a starting point for protein engineering through yeast surface display to enhance receptor-binding affinity. We recovered Fc variants from this approach that demonstrated FcγRIIIa binding affinities comparable to the starting sequence and thus serve as a proof-of-principle for this strategy.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576861","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":"pIgR Stem Zone-Targeted Nanobodies as Apical-to-Basolateral Carriers for Inhaled Biologic Delivery Across Mucosal Barriers.","authors":"Aidong Qiu, Ruiyuan Wang, Yangyingjie Bai, Bowen Zhang, Xinyu He, Jiani Xie, Jianghai Liu","doi":"10.3390/antib15040053","DOIUrl":"10.3390/antib15040053","url":null,"abstract":"<p><strong>Background: </strong>The mucosal barrier presents a significant challenge for non-invasive delivery of macromolecular therapeutics, often requiring administration with poor bioavailability and increased toxicity risks. The polymeric immunoglobulin receptor (pIgR) contains an extracellular secretory component (SC) for immunoglobulin binding and a membrane-anchored stem domain capable of apical-to-basolateral transcytosis. We hypothesized that targeting the stem domain could enable active drug transport across mucosal barriers.</p><p><strong>Methods: </strong>Using phage display, we identified four high-affinity nanobodies against human and murine pIgR. Two lead candidates (3LTHMP-4 and 3LTHMP-5) demonstrated efficient apical-to-basolateral transport in vitro (Transwell assays) and in vivo (fluorescence imaging). Engineered bispecific antibodies fusing these nanobodies with anti-IL-5 mAb reslizumab were administered via inhalation in a murine asthma model at one-tenth the intraperitoneal reslizumab dose.</p><p><strong>Resluts: </strong>The bispecific antibodies showed significant therapeutic efficacy, while reslizumab alone at equivalent concentrations failed to demonstrate efficacy. Hydrogen-Deuterium Exchange Mass Spectrometry (HDX-MS) revealed that both 3LTHMP-4 and 3LTHMP-5 specifically bind to the pIgR stem domain (residues 578-612), a region distinct from the dimeric IgA binding site.</p><p><strong>Conclusions: </strong>These findings suggest that stem domain-specific binding may facilitate transport across the mucosal barrier while preserving native receptor physiology, offering a potential strategy for effective transmucosal delivery of biologics.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576271","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":"Rational Design and Characterization of a Mutated Nanobody for Specific Targeting of Heparan Sulfate.","authors":"Junfang Hao, Qian Xu, Yanyan Cui, Wenlong Wang, Kai Huang","doi":"10.3390/antib15040052","DOIUrl":"10.3390/antib15040052","url":null,"abstract":"<p><strong>Background: </strong>Viral attachment mediated by host cell surface receptors is the first step in viral infection. As a key cell surface receptor, heparan sulfate (HS) mediates the attachment and entry of numerous non-enveloped viruses in livestock, thereby serving as a crucial molecular target for studying virus-host interactions.</p><p><strong>Methods: </strong>Based on the structural scaffold of a nanobody (Nb; PDB: 7TJC), we rationally designed and constructed a mutant Nb targeting HS, designated HS-Mut-Nb1, using molecular docking, site-directed mutagenesis, molecular dynamics (MD) simulations, and experimental characterization.</p><p><strong>Results: </strong>Molecular docking indicated that the active site of wild-type Nb for HS binding was located within the cavity jointly formed by the complementarity-determining region 3 (CDR3) and the framework regions (FRs) of the wild-type Nb. A comprehensive analysis integrating virtual alanine scanning, site-directed mutagenesis, and MD simulations revealed that the combination of three point mutations (Phe47Arg, Asp99Tyr, and Tyr108Pro) significantly enhanced the binding affinity of Mut-Nb1 for HS, with a calculated binding free energy (ΔG) of -83.26 ± 3.06 kcal/mol. Enzyme-linked immunosorbent assay (ELISA) results further confirmed that Mut-Nb1 exhibited high affinity for HS (<i>K</i>_D = 65.87 nM) and specificity (positive/negative ratio, P/N = 3.84; cross-reactivity, CR < 6.60%).</p><p><strong>Conclusions: </strong>This study not only provides novel candidate molecules for elucidating the mechanism of HS-virus interactions and developing related inhibitors but also offers a reference for the rapid construction of mutant Nbs.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13398245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576536","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":"Characterization of Anti-Phospholipid Antibodies in Lyme Borreliosis Using In-House Developed ELISAs.","authors":"Polona Žigon, Katja Lakota, Katarina Ogrinc, Petra Bogovič, Franc Strle","doi":"10.3390/antib15030051","DOIUrl":"10.3390/antib15030051","url":null,"abstract":"<p><strong>Objectives: </strong><i>Borrelia burgdorferi</i> sensu lato, a spirochete bacterium responsible for Lyme borreliosis-the most common tick-borne infection in North America and Europe-can trigger the production of antiphospholipid antibodies. These antibodies target host lipids such as cardiolipin (CL), phosphatidic acid (PA), phosphatidylcholine (PC), and phosphatidylserine (PS), which the spirochete incorporates into its membrane from the surrounding environment. Although antiphospholipid antibodies are typically associated with antiphospholipid syndrome (APS), they may also arise during infections, including Lyme borreliosis. This study aimed to develop and optimize several enzyme-linked immunosorbent assays (ELISAs) for measuring various antiphospholipid antibodies in patients with Lyme borreliosis.</p><p><strong>Methods: </strong>Thirty patients diagnosed with Lyme borreliosis were enrolled: ten with solitary erythema migrans (EM), ten with multiple EM (MEM), and ten with late manifestations known as acrodermatitis chronica atrophicans (ACA). Forty healthy blood donors served as controls. Four distinct antiphospholipid antibody ELISAs were developed, each using a different phospholipid coating: CL, PA, PC, and PS. Serum of APS patient was used as a positive control and for standard curve generation.</p><p><strong>Results: </strong>All four ELISAs were successfully established and demonstrated good measurement precision. Significant differences in antiphospholipid antibody levels and positivity rates were observed between Lyme borreliosis patients and healthy blood donors. Notably, levels of antibodies directed against PA (aPA), PC (aPC), and PS (aPS), both IgG and IgM, were significantly higher in patients with late Lyme borreliosis, manifested as ACA, compared to healthy blood donors. In contrast, anti-CL (aCL) levels did not differ significantly between groups. Patients with ACA also showed the highest frequency of multiple antiphospholipid antibody positivity, with 7 out of 10 patients testing positive for three or more antiphospholipid antibodies.</p><p><strong>Conclusions: </strong>Accurate and precise in-house ELISAs for the detection of aCL, aPA, aPC, and aPS using APS sera as standard material were developed and validated for the analysis of samples of patients with Lyme borreliosis. Our data suggest that antiphospholipid antibody levels-specifically aPA, aPC, and aPS-differ across clinical manifestations of Lyme borreliosis, with the greatest increases observed in patients with ACA.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13296186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315346","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":"Anti-Type I Interferon Autoantibodies in COVID-19 and Systemic Lupus Erythematosus: A Comparative Review.","authors":"Xin Rong Lim, Ryan Xuan Wei Teo, Rae Yi Xin Par, Bernard Pui Lam Leung","doi":"10.3390/antib15030050","DOIUrl":"10.3390/antib15030050","url":null,"abstract":"<p><p>Type I interferons (IFN-I), including IFN-α, IFN-β, and IFN-ω, are central to antiviral defence and immune regulation. Autoantibodies targeting IFN-I (anti-IFN-I AAbs) have emerged as key pathogenic factors in severe coronavirus disease 2019 (COVID-19) and are detectable in systemic lupus erythematosus (SLE), a prototypic IFN-driven autoimmune disease. Here we compare the prevalence and clinical impact of anti-IFN-I autoantibodies (Aabs) in COVID-19 and SLE based on a structured review of 53 studies from 2014 to 2025 and highlight the clinical associations and therapeutic opportunities presented by these autoantibodies. In COVID-19, neutralising anti-IFN-α and/or anti-IFN-ω AAbs were consistently associated with severe disease and impaired antiviral responses, particularly in older male populations. In SLE, anti-IFN-α AAbs were variably detected; neutralising antibodies were associated with reduced interferon gene signatures in some cohorts but inconsistent correlations with disease activity. Therapeutically, anti-IFN-I AAbs in COVID-19 may inform risk stratification and early antiviral strategies, whereas in SLE, IFN-α blockade, including IFN-α kinoid vaccination, demonstrates modulation of IFN signatures but variable clinical benefit. Notably, these findings reveal an immunological paradox: the same neutralising mechanism that impairs antiviral defence in COVID-19 may attenuate chronic IFN-driven inflammation in SLE. Taken together, anti-IFN-I AAbs exert context-dependent effects: pathogenic in acute viral infection yet potentially modulatory in chronic IFN-driven autoimmunity. Prospective longitudinal studies are required to further clarify their translational utility and long-term clinical impact.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13296295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315307","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":"Improving Gallbladder Cancer Outcomes with Antibody-Based Therapies and Immunological Profiling: A Literature Review.","authors":"Christian Caglevic, Mario Alex Contreras-Torrez, Felipe Reyes-Cosmelli, Rodrigo Uribe-Maturana, Mauricio Mahave, Nicole Caire, Luis Villanueva-Olivares, Fernando Cid, Alvaro Lladser, Jorge Sapunar","doi":"10.3390/antib15030049","DOIUrl":"10.3390/antib15030049","url":null,"abstract":"<p><p>Gallbladder cancer (GBC) is an aggressive tumor that, together with the cholangiocarcinomas, constitutes the spectrum of biliary tract cancer (BTC). These tumors are characterized by a frequently late diagnosis, marked genomic heterogeneity, variable response to cytotoxic therapies, and poor overall survival in advanced stages. Nevertheless, the characterization of the tumor microenvironment (TME) and the identification of actionable molecular targets have driven the development of biological therapies. This review summarizes current and emerging evidence on monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates (ADCs) in the management of GBC. The analysis addresses the early exploration of autoantibodies as potential diagnostic biomarkers, mechanistic hypotheses of immune evasion, and the clinical translation of targeted agents in the metastatic setting. Additionally, we critically discuss the extrapolation of data from global BTC trials to the specific GBC setting, the integration of population genetics into epidemiological studies such as the EULAT Eradicate GBC initiative, and the preliminary status of immunotherapy in perioperative scenarios.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"15 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13295283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315428","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}