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SARS-CoV-2 Infection and COVID-19 Vaccine Antibody Responses in Two Canadian Cohorts of Persons Living with HIV
IMGT^® Nomenclature of Immunoglobulins (IG) or Antibodies and T Cell Receptors (TR): A Common Language for Immunoinformatics and Artificial Intelligence (AI)
Post-Chemotherapy Antibody-Based Continuation and Maintenance Strategies in HER2-Positive Metastatic Breast Cancer: A Translational Narrative Review
Brain Delivery of Antibody-Derived Biologicals for Alzheimer’s Disease: An Updated Narrative Review
Two Highly Specific Mouse Monoclonal Antibodies to the Putative C-Telopeptide of Human Collagen XIα1, a Cancer Biomarker

Journal Description

Antibodies

Antibodies is an international, peer-reviewed, open access journal on immunoglobulins, published bimonthly online by MDPI.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, ESCI (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
Journal Rank: CiteScore - Q2 (Immunology and Allergy)
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 22.7 days after submission; acceptance to publication is undertaken in 4.8 days (median values for papers published in this journal in the first half of 2026).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Journal Cluster of Immunology: Vaccines, Antibodies, Immuno, Rheumato, Lymphatics and
Inflammation Journal.

Impact Factor: 3.3 (2025); 5-Year Impact Factor: 4.1 (2025)

Imprint Information Journal Flyer Open Access ISSN: 2073-4468

Latest Articles

19 pages, 1690 KB

Open AccessArticle

An Open-Label, Comparative, Parallel Clinical Trial of the Safety, Pharmacokinetics and Immunogenicity of the Ustekinumab Biosimilar GNR-068 and the Originally Developed Ustekinumab as a Reference Drug After a Single Subcutaneous Administration in Healthy Male Volunteers

by Ivan Lyagoskin, Alena Agafonova, Ivan Shevchenko, Nina Akhtyamova-Givirovskaya, Oksana Markova, Marina Pantyushenko, Rakhim Shukurov and Ravil Khamitov

Antibodies 2026, 15(4), 77; https://doi.org/10.3390/antib15040077 - 12 Aug 2026

GNR-068 is a proposed biosimilar to the ustekinumab reference product (RP), which works through the antagonism of interleukin 12 and interleukin 23. Ustekinumab RP is used for the treatment of chronic inflammatory conditions, including certain forms of plaque psoriasis, psoriatic arthritis, Crohn’s disease, [...] Read more.

GNR-068 is a proposed biosimilar to the ustekinumab reference product (RP), which works through the antagonism of interleukin 12 and interleukin 23. Ustekinumab RP is used for the treatment of chronic inflammatory conditions, including certain forms of plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. Objectives: The purpose of the study is to study the safety, pharmacokinetics, and immunogenicity of the ustekinumab biosimilar GNR-068 and the reference drug Stelara^® after a single subcutaneous administration in healthy male volunteers. Methods: This was an open-label, randomized, comparative, parallel-group clinical trial of the safety, pharmacokinetics (PK), and immunogenicity of GNR-068 (JSC GENERIUM) and Stelara^® (Manufacturer: Silag AG, Switzerland; RU Holder: JOHNSON & JOHNSON) after a single subcutaneous administration of 45 mg in healthy volunteers. During the trial, 146 volunteers were screened, and 122 were randomized. Results: The results showed that PK similarity was established based on 90% confidence intervals (CIs) for the ratios of geometric means of the primary endpoints of area under the concentration-time curve from time 0 extrapolated to infinity (AUC_0–∞) and maximum observed serum concentration (Cmax) being contained within the pre-specified margin of 80.00–125.00%. The incidence of total ADA was lower in the GNR-068 group compared with the reference product group. Adverse events were similar between treatment groups and consistent with the safety profile of the ustekinumab RP. Conclusions: These results indicate that GNR-068 and the ustekinumab RP share similar PK and safety profiles. Full article

(This article belongs to the Special Issue Immune Phenomena in Autoimmune Skin Disorders)

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18 pages, 10673 KB

Open AccessArticle

A CSF-1R Ig4-5 Domain-Targeting Antibody for the Treatment of Idiopathic Pulmonary Fibrosis

by Wusong Luo, Zhe Shao, Tao Wang, Kenghoe Lok, Rongjing Zhang and Yao Li

Antibodies 2026, 15(4), 76; https://doi.org/10.3390/antib15040076 - 11 Aug 2026

Background: Idiopathic pulmonary fibrosis (IPF) is closely associated with fibroblast proliferation, macrophage polarization, and the accumulation of extracellular matrix (ECM). Targeting CSF-1R can rebalance macrophages, reduce ECM deposition, and block pro-fibrotic signaling. Methods: A Fab fragment targeting CSF-1R was screened via phage display. [...] Read more.

Background: Idiopathic pulmonary fibrosis (IPF) is closely associated with fibroblast proliferation, macrophage polarization, and the accumulation of extracellular matrix (ECM). Targeting CSF-1R can rebalance macrophages, reduce ECM deposition, and block pro-fibrotic signaling. Methods: A Fab fragment targeting CSF-1R was screened via phage display. After sequence optimization, it was constructed into an IgG1 antibody (BC006). In vitro activity, domain binding, and signaling blockade were investigated, and in vitro safety indicators were evaluated. Efficacy was assessed using an induced IPF organoid-on-a-chip and bleomycin-induced mouse model. In vivo safety evaluation was conducted in cynomolgus monkeys. Results: BC006 showed an EC₅₀ value of 226 ± 57 nM and a KD of 30 ± 2 nM. It specifically bound to the Ig4-5 domain of CSF-1R by inhibiting receptor dimerization without blocking ligand binding. It could dose-dependently inhibit the differentiation of monocytes into M2 macrophages and exert anti-IPF effects. In the induced IPF organoid-on-a-chip model, BC006 maintained lung barrier function and decreased α-SMA and Collagen I. It also improved lung function and attenuated the degree of fibrosis in the mouse model. Moreover, BC006 had no ADCC, CDC, cytokine release, or hemagglutination, and demonstrated favorable safety profiles in cynomolgus monkeys. Conclusions: BC006 is a novel anti-fibrosis antibody specifically targeting the CSF-1R Ig4-5 domain and offers a new therapeutic strategy for IPF. Full article

(This article belongs to the Section Antibody-Based Therapeutics)

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21 pages, 3046 KB

Open AccessReview

Advances in the Development of a Universal Influenza Vaccine

by Preanka Mudaly, Max Lee, Aishwarya Bhatta and Craig Thompson

Antibodies 2026, 15(4), 75; https://doi.org/10.3390/antib15040075 - 11 Aug 2026

Influenza remains a persistent global health threat, accounting for an estimated one billion infections and 350,000–600,000 deaths worldwide annually. Beyond substantial mortality and morbidity, influenza imposes major socio-economic costs through healthcare utilisation and productivity losses, amounting to tens of billions of dollars each [...] Read more.

Influenza remains a persistent global health threat, accounting for an estimated one billion infections and 350,000–600,000 deaths worldwide annually. Beyond substantial mortality and morbidity, influenza imposes major socio-economic costs through healthcare utilisation and productivity losses, amounting to tens of billions of dollars each year. Current seasonal vaccination strategies are constrained by rapid antigenic evolution, which necessitates frequent vaccine reformulation and contributes to suboptimal vaccine efficacy across seasons. These drawbacks highlight the need for a universal influenza vaccine (UIV) that protects against all seasonal and potential pandemic influenza strains via a single dose. This review evaluates the feasibility of a UIV as an alternative to a seasonal influenza vaccine (SIV) by consolidating evidence from current UIV candidates in preclinical and clinical development across a diverse range of platforms and target epitopes. Preclinical studies and clinical trials have demonstrated the safety and tolerability of multiple candidates, as well as their ability to elicit broadly cross-reactive immune responses. However, several challenges remain regarding the long-term efficacy of these vaccines. In particular, pre-existing host immunity can shape subsequent vaccine responses, with immune imprinting introducing biases toward previously encountered influenza strains, potentially reducing vaccine effectiveness. In addition, the genetic plasticity of influenza viruses, driven by ongoing mutations and genetic reassortment, raises concerns about the ability of a single vaccine formulation to maintain broad and durable protection. Overall, several UIV candidates have shown promising early results. Although ecological and immunological barriers remain, a UIV could become a viable alternative to, or eventual replacement, for SIVs. Full article

(This article belongs to the Section Antibody-Based Therapeutics)

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12 pages, 1035 KB

Open AccessArticle

Real-World Effectiveness of Secukinumab in Congenital Ichthyoses: A Retrospective Monocentric Case Series

by Orsola Crespi, Umberto Santaniello, Luca Cangialosi, Ambra Bonvicino, Michela Ortoncelli, Francois Rosset, Luca Mastorino, Simone Ribero and Pietro Quaglino

Antibodies 2026, 15(4), 74; https://doi.org/10.3390/antib15040074 - 11 Aug 2026

Background/Objectives: Congenital ichthyoses (CI) are inherited disorders of keratinization characterized by epidermal barrier dysfunction, abnormal desquamation, and variable degrees of inflammation. Increasing evidence suggests a role for IL-23/Th17-mediated immune dysregulation in some CI subtypes, providing a rationale for targeted biologic therapies. Secukinumab, an [...] Read more.

Background/Objectives: Congenital ichthyoses (CI) are inherited disorders of keratinization characterized by epidermal barrier dysfunction, abnormal desquamation, and variable degrees of inflammation. Increasing evidence suggests a role for IL-23/Th17-mediated immune dysregulation in some CI subtypes, providing a rationale for targeted biologic therapies. Secukinumab, an anti-IL-17A monoclonal antibody, has emerged as a potential therapeutic option, although real-world evidence remains limited. This study evaluated the effectiveness of secukinumab in adult patients with severe CI. Methods: We performed a retrospective monocentric case series including eight adult patients with severe congenital ichthyosis treated with secukinumab for at least six months and followed for up to 56 months. Clinical outcomes included Investigator Global Assessment (IGA) scores for erythema, scaling, scalp involvement, and palmoplantar hyperkeratosis, together with pruritus assessed by Numeric Rating Scale (NRS). Results: Erythema and scaling showed most of their improvement during the first six months of treatment, after which mean clinical scores remained relatively stable throughout follow-up. At the last available assessment, improvement rates were 100% for erythema, 87.5% for trunk and limb scaling, 100% for scalp scaling, and 75% for palmoplantar hyperkeratosis. Hyperkeratosis showed a less pronounced response than inflammatory manifestations. Pruritus improved within the first 3–4 months of treatment and was sustained over time, with mean NRS scores decreasing from 6.5 at baseline to below 4 within 3–4 months. No discontinuations due to adverse events or lack of efficacy were recorded. Conclusions: Secukinumab was associated with clinically meaningful improvements in inflammatory manifestations of CI, particularly erythema and pruritus, while showing a more limited effect on hyperkeratotic features. These findings support the potential role of IL-17 inhibition in selected CI phenotypes. Full article

(This article belongs to the Section Antibody-Based Therapeutics)

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13 pages, 458 KB

Open AccessArticle

Acetylcholine Receptor Antibody Positivity, RNST Abnormality, and Thymoma Predict Generalization in Ocular Myasthenia Gravis: A South Korean Cohort Study

by Hyun Jin Shin, Chaerin Kwon and Jeeyoung Oh

Antibodies 2026, 15(4), 73; https://doi.org/10.3390/antib15040073 - 11 Aug 2026

Background: Ocular myasthenia gravis (OMG) can remain restricted to ocular symptoms or progress to generalized myasthenia gravis (GMG). However, the rate of generalization and its predictors may vary across populations, and data on South Korean patients remain inadequate. This study investigated the conversion [...] Read more.

Background: Ocular myasthenia gravis (OMG) can remain restricted to ocular symptoms or progress to generalized myasthenia gravis (GMG). However, the rate of generalization and its predictors may vary across populations, and data on South Korean patients remain inadequate. This study investigated the conversion rate from OMG to GMG and identified clinical, serologic, electrophysiologic, and thymic predictors of this generalization in a South Korean cohort. Methods: This retrospective cohort study included 89 patients who initially presented with OMG and were followed up for at least 2 years. The primary outcome was conversion to GMG during follow-up. The investigated predictors included demographic variables, initial ocular manifestations, acetylcholine receptor antibody (AChR-Ab) status and titer, repetitive nerve stimulation test (RNST) findings, thymic abnormalities, and immunosuppressive treatment. Kaplan–Meier analyses and Cox proportional-hazards models were used to evaluate the GMG-free survival rate and risk factors for conversion. Results: During follow-up, 10 patients (11.2%) progressed to GMG, with this conversion occurring within 2 years in 8 patients (9.0%). All converters were AChR-Ab positive. AChR-Ab positivity, RNST positivity, thymic abnormality, and thymoma were associated with GMG conversion in univariable analyses. RNST positivity in any tested muscle (hazard ratio [HR] = 12.66, 95% confidence interval [CI] = 2.68–59.76, p = 0.001) and thymoma (HR = 10.67, 95% CI = 3.06–37.27, p < 0.001) was associated with generalization. These associations persisted in the restricted multivariable Cox model. Conclusions: The rate of GMG conversion was relatively low in this South Korean OMG cohort, and most conversions occurred within 2 years. The presence of AChR-Ab positivity, RNST abnormality, or thymoma may characterize high-risk patients who require closer monitoring during the early disease course. Full article

(This article belongs to the Section Antibody-Based Diagnostics)

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13 pages, 263 KB

Open AccessArticle

Endogenous Sex Hormones Explain Variation in Long-Term SARS-CoV-2 Antibody Persistence Beyond Biological Sex

by Nicole Ivaska and Laura Rothschild

Antibodies 2026, 15(4), 72; https://doi.org/10.3390/antib15040072 - 7 Aug 2026

Background: Sex-related differences in SARS-CoV-2 viral susceptibility, severity, and recovery are prevalent. Factors such as age and biological variation provide some explanation for immune response, yet the use of biological sex as a variable may limit understanding of underlying individual mechanisms related [...] Read more.

Background: Sex-related differences in SARS-CoV-2 viral susceptibility, severity, and recovery are prevalent. Factors such as age and biological variation provide some explanation for immune response, yet the use of biological sex as a variable may limit understanding of underlying individual mechanisms related to endocrine–immune function involved in long-term immune memory. Endogenous sex hormone concentrations provide a means to assess the magnitude or durability of antibody persistence and disease recovery. Objective: This study examined salivary concentrations of 17β-estradiol and testosterone, as well as the number of weeks since prior SARS-CoV-2 viral infection. The study aimed to determine whether endogenous sex hormones contributed additional explanatory value to antibody persistence beyond biological sex. Methods: A cross-sectional study included 75 college students (63% female) who reported weeks since previous SARS-CoV-2 infection (M = 15.41, SD = 7.13), confirmed through a positive SARS-CoV-2 anti-N rapid antibody test. Participants provided saliva samples, which were tested for concentration of 17β-estradiol and testosterone. Hierarchical multiple regression analyses examined the effects of biological sex and endogenous sex hormones on the persistence of SARS-CoV-2 antibodies following natural infection. Results: 17β-estradiol was the strongest positive predictor of SARS-CoV-2 antibody persistence (β = 0.63, p < 0.001). Departing from previous findings, biological sex was not a significant predictor of antibodies targeting the SARS-CoV-2 N protein. Conclusions: Findings underscored the role of estradiol on immune recovery in a healthy young adult population. Individual hormone variation appears more informative than sex classification for understanding antibody persistence and immune response. Full article

(This article belongs to the Special Issue Antiviral Antibody Immune Responses in the Context of Vaccination and Infection)

9 pages, 480 KB

Open AccessReview

Multiple Modes of Action of Anti-TNF-α Antibodies for Inflammatory Bowel Diseases Beyond TNF-α Neutralization

by Tomohiro Watanabe and Masatoshi Kudo

Antibodies 2026, 15(4), 71; https://doi.org/10.3390/antib15040071 - 6 Aug 2026

Inflammatory bowel diseases (IBDs), chronic inflammatory disorders of the gastrointestinal tract, are classified into Crohn’s disease (CD) and ulcerative colitis (UC). Despite differing clinical manifestations, both CD and UC share a common immunopathogenesis, involving excessive production of proinflammatory cytokines by macrophages and dendritic [...] Read more.

Inflammatory bowel diseases (IBDs), chronic inflammatory disorders of the gastrointestinal tract, are classified into Crohn’s disease (CD) and ulcerative colitis (UC). Despite differing clinical manifestations, both CD and UC share a common immunopathogenesis, involving excessive production of proinflammatory cytokines by macrophages and dendritic cells. Tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12), and IL-23 are prototypical proinflammatory cytokines associated with CD and UC development, and biologics targeting these cytokines are widely used for treating patients with IBD. Antibodies (Abs) against IL-12 and IL-23 decrease intestinal inflammation by binding to the soluble forms of IL-12 and IL-23, respectively. Notably, anti-TNF-α Abs induce remission by neutralizing soluble TNF-α as well as membrane-bound TNF-α (mTNF-α). The binding of anti-TNF-α Abs to mTNF-α enables the diverse functions of IBD-specific TNF-α-inhibitors. Multiple modes of action of anti-TNF-α Abs for IBD include complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity, apoptosis of cells expressing mTNF-α, apoptosis of lamina propria T cells, and induction of regulatory T cells and macrophages. In this article, we introduce the diverse actions of anti-TNF-α Abs beyond TNF-α neutralization and discuss how these unique properties of anti-TNF-α Abs contribute to the efficient downregulation of IBD-associated inflammation. Full article

(This article belongs to the Section Antibody-Based Therapeutics)

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18 pages, 889 KB

Open AccessReview

Antibody-Dependent and Antibody-Independent Hemolysis in Sickle Cell Disease

by Raeshun T. Glover and Robert W. Maitta

Antibodies 2026, 15(4), 70; https://doi.org/10.3390/antib15040070 - 6 Aug 2026

Sickle cell disease (SCD) represents one of the most complex hematological diseases leading to a lifetime of physiological crises characterized by chronic hemolysis, inflammation, hypoxia, and anemia with changes to body systems that result in patients having shorter lifespans. Transfusions, either simple or [...] Read more.

Sickle cell disease (SCD) represents one of the most complex hematological diseases leading to a lifetime of physiological crises characterized by chronic hemolysis, inflammation, hypoxia, and anemia with changes to body systems that result in patients having shorter lifespans. Transfusions, either simple or as part of red cell exchanges, are often needed to lower the hemoglobin S levels to minimize the possibility of sickling of red blood cells (RBCs) and provide patients with greater oxygen carrying capacity. However, hemolysis in SCD patients is a common finding/presentation of the disease, especially during acute crises. One of the ensuing complications of a life of transfusions is the development of alloantibodies to RBC antigens despite partial or extended matching. This is further complicated by formation of autoantibodies even in the setting of RBC matching, suggesting that a hyperactive immune response in these patients is primed to respond with formation of antibodies. In a sub-cohort of patients, no antibodies are detected despite extensive investigation, and the ensuing hemolysis requires minimizing exposure to RBC transfusions to avoid developing a greater hemolytic process. Instead, immunosuppression or monoclonals that target complement or cytokines shown to be involved in this type of hemolysis are necessary. In this context, this narrative review will present antibody-dependent and antibody-independent mechanisms of hemolysis in SCD, including therapeutic approaches that target specific areas of the immune response that are possibly involved in the destruction of RBCs. Full article

(This article belongs to the Section Humoral Immunity)

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19 pages, 1294 KB

Open AccessReview

Bispecific Antibodies for Acute Myeloid Leukemia: From Bone Marrow Immune Niche to Clinical Translation

by Antonella Bruzzese, Enrica Antonia Martino, Santino Caserta, Maria Eugenia Alvaro, Nicola Amodio, Eugenio Lucia, Virginia Olivito, Caterina Labanca, Francesco Mendicino, Fortunato Morabito, Ernesto Vigna and Massimo Gentile

Antibodies 2026, 15(4), 69; https://doi.org/10.3390/antib15040069 - 4 Aug 2026

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid blasts and the persistence of leukemic stem cells (LSCs) within a profoundly remodeled bone marrow (BM) microenvironment. Despite advances in molecular stratification and the introduction of targeted [...] Read more.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid blasts and the persistence of leukemic stem cells (LSCs) within a profoundly remodeled bone marrow (BM) microenvironment. Despite advances in molecular stratification and the introduction of targeted agents, long-term outcomes remain unsatisfactory, particularly in older and high-risk patients. Increasing evidence indicates that leukemogenesis and treatment resistance are critically sustained by a permissive immune milieu, in which LSCs, myeloid-derived suppressor cells, leukemia-associated macrophages, and dysfunctional T and NK cells shape an immunosuppressive “leukemic niche.” This evolving understanding has renewed interest in immune-based strategies capable of restoring effective antitumor immunity. Bispecific antibodies (bsAbs) are engineered molecules designed to engage AML-associated antigens while simultaneously recruiting and activating immune effector cells, most commonly T cells or NK cells. By promoting immune synapse formation independently of major histocompatibility complex expression and conventional co-stimulatory pathways, bsAbs can overcome several mechanisms of immune escape. In this review, we summarize the biological rationale for immunotherapy in AML, with a focus on the role of the BM microenvironment and immune dysregulation. We then discuss the structural and functional properties of IgG-like and non-IgG-like bsAbs, key antigenic targets such as CD33, CD123, CD70 and others, and the main T-cell- and NK-cell-engaging platforms under clinical investigation. Finally, we highlight emerging clinical data, principal toxicities, and the challenges of integrating bsAbs into existing treatment algorithms, including combinations with hypomethylating agents, BCL-2 inhibitors, and allogeneic stem cell transplantation. A deeper understanding of AML immune biology and antigen expression patterns will be essential to optimize bsAb design, maximize therapeutic benefit, and minimize on-target off-tumor toxicity. Full article

(This article belongs to the Section Antibody-Based Therapeutics)

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21 pages, 2808 KB

Open AccessArticle

Correlation of AHR Activation-Induced Suppression of PWM-Stimulated IgG and IgG-Triggered Signaling in Human PBMCs

by Arpita Deb and Barbara L. F. Kaplan

Antibodies 2026, 15(4), 68; https://doi.org/10.3390/antib15040068 - 4 Aug 2026

Background/Objectives: Aryl hydrocarbon receptor (AHR) ligands are known to suppress antibody production. However, it remains unclear whether this suppression translates into altered antibody-mediated Fcγ receptor signaling in human cells. This study aimed to investigate the effects and mechanisms by which AHR ligands regulate [...] Read more.

Background/Objectives: Aryl hydrocarbon receptor (AHR) ligands are known to suppress antibody production. However, it remains unclear whether this suppression translates into altered antibody-mediated Fcγ receptor signaling in human cells. This study aimed to investigate the effects and mechanisms by which AHR ligands regulate antibody production and antibody-triggered responses in human peripheral blood mononuclear cells (PBMCs). Methods: PBMCs were isolated from blood obtained from anonymous healthy donors. PBMCs were stimulated with pokeweed mitogen (PWM) to induce IgG1 production or Strept-Biotin IgG1/IgG2 immune complexes to induce antibody-triggered signaling. Before any stimulation, cells were pretreated with vehicle (0.01% DMSO) or AHR ligands TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), ITE (2-(1H-indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl ester), or FICZ (6-formylindolo[3,2-b]carbazole), or the proligand I3C (indole-3-carbinol). Results: Our data revealed that PWM stimulation significantly increased IL6 and IL1B gene expression and PWM-induced IL-6 cytokine secretion, which was significantly suppressed by TCDD, ITE, FICZ, and I3C. However, only TCDD was able to suppress PWM-stimulated IgG1 antibody production. Transcriptomic analysis using I3C revealed upregulated AHR-responsive genes such as CYP1A1, CYP1B1, AHRR and TIPARP in PWM-stimulated human PBMCs. Notably, I3C downregulated genes TRAPPC9 and C1QTNF3, which play a role in NF-κB-associated inflammatory signaling. It also revealed potential sex differences in I3C-mediated gene modulation associated with B cell function, Ig expression, FcγR signaling, and inflammatory pathways. Lastly, IgG1 and IgG2 immune complex-stimulated IL-6 cytokine secretion was significantly suppressed by TCDD, whereas I3C showed modest, although not statistically significant, suppression. Conclusions: Overall, these findings demonstrate that AHR activation by TCDD suppressed antibody production and IgG-mediated immune signaling in human PBMCs. Full article

(This article belongs to the Section Humoral Immunity)

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24 pages, 1122 KB

Open AccessReview

Functional Parameters of Hybridoma Cells: Methods of Evaluation and Biotechnological Relevance

by Tatiana Bezukladnikova, Svetlana Zamorina, Sergey Lazarev and Mikhail Rayev

Antibodies 2026, 15(4), 67; https://doi.org/10.3390/antib15040067 - 4 Aug 2026

Hybridoma technology remains one of the most reliable and widely used platforms for generating highly specific monoclonal antibodies for use in diagnostics, fundamental research, and clinical practice. Moreover, the combination of unlimited proliferative capacity with the preservation of a key B-lymphocyte function, antibody [...] Read more.

Hybridoma technology remains one of the most reliable and widely used platforms for generating highly specific monoclonal antibodies for use in diagnostics, fundamental research, and clinical practice. Moreover, the combination of unlimited proliferative capacity with the preservation of a key B-lymphocyte function, antibody production, enables hybridoma cells to support a comprehensive functional evaluation of cellular responses. Thus, by integrating analysis of proliferation, viability, and productivity, hybridoma-based approaches enable the detection of differential modulatory effects and offer a nuanced assessment of compound bioactivity. This review provides a comprehensive analysis of the functional parameters of hybridoma cells: viability, proliferation, and productivity, as well as the methods used for their evaluation. The main stages of hybridoma cell generation, advances in hybridoma technology, and current applications of hybridoma cells are also reviewed. A key aspect of this review is the differential modulation of functional parameters of hybridoma cells. Modulation of culture conditions and bioactive compounds can differentially influence growth dynamics and specific antibody yield, often revealing an inverse relationship between proliferation and productivity. Full article

(This article belongs to the Section Antibody Discovery and Engineering)

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14 pages, 10261 KB

Open AccessArticle

Fc-Silenced CD89 × EGFR Bispecific Antibodies Promote Neutrophil and Macrophage Antitumor Activity

by Felix Meiser, Julia Harwardt, Christoph Hahn, Marta Lustig, Thomas Valerius and Harald Kolmar

Antibodies 2026, 15(4), 66; https://doi.org/10.3390/antib15040066 - 29 Jul 2026

Background/Objectives: CD89 (FcaRI), the receptor for immunoglobulin A (IgA), is expressed on myeloid cells, including neutrophils, monocytes, and macrophages. It is known to mediate potent effector functions against tumor cells, but the clinical development of IgA-based therapeutics is hindered by manufacturing challenges and [...] Read more.

Background/Objectives: CD89 (FcaRI), the receptor for immunoglobulin A (IgA), is expressed on myeloid cells, including neutrophils, monocytes, and macrophages. It is known to mediate potent effector functions against tumor cells, but the clinical development of IgA-based therapeutics is hindered by manufacturing challenges and IgA’s short plasma half-life. Methods: Using yeast display, we generated EGFR × CD89 bispecific common light chain antibodies and investigated their biophysical properties, neutrophil-mediated cytotoxicity and macrophage phagocytosis in vitro. Results: CD89-targeting constructs induced potent neutrophil cytotoxicity and macrophage phagocytosis in vitro. A symmetric 2 + 2 IgG1 Fc-silenced variant showed the most consistent potency across neutrophil and macrophage effector functions. Fc silencing enhanced neutrophil ADCC and did not induce detectable neutrophil or PBMC fratricide under the conditions tested, suggesting a limited propensity for off-target immune cell killing. Conclusions: These findings support further preclinical evaluation of CD89-targeting bispecific antibodies and indicate that Fc silencing may differentially shape neutrophil- and macrophage-mediated antitumor activity. Full article

(This article belongs to the Section Antibody Discovery and Engineering)

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18 pages, 11006 KB

Open AccessArticle

Biopsy-Confirmed Acute Interstitial Nephritis in Patients Treated with Immune Checkpoint Inhibitors: A Single-Center Retrospective Case Series

by Ioannis Ogrotis, Konstantinos Drouzas, Evangelia Pantzopoulou, Petros Nikolopoulos, Ioannis Kotsantis, Amanda Psyrri, George Liapis and Sophia Lionaki

Antibodies 2026, 15(4), 65; https://doi.org/10.3390/antib15040065 - 27 Jul 2026

Background/Objectives: Acute interstitial nephritis (AIN) is a cause of acute kidney injury (AKI) during immune checkpoint inhibitor (ICI) therapy, but biopsy-confirmed data are limited. We estimated institutional proportions of biopsy-confirmed AIN clinically attributed to ICI exposure (ICI-AIN) and characterized its presentation, pathology, [...] Read more.

Background/Objectives: Acute interstitial nephritis (AIN) is a cause of acute kidney injury (AKI) during immune checkpoint inhibitor (ICI) therapy, but biopsy-confirmed data are limited. We estimated institutional proportions of biopsy-confirmed AIN clinically attributed to ICI exposure (ICI-AIN) and characterized its presentation, pathology, treatment, and renal outcomes. Methods: We retrospectively reviewed native renal biopsies performed at Attikon University Hospital from February 2021 through December 2025. Cases were included when ICI exposure preceded AKI and the treating nephrology team documented clinicopathologic attribution to ICI exposure. Results: AIN was identified in 15 of 339 native renal biopsies; 12 cases were attributed to ICI exposure, representing 3.5% of native renal biopsies and 0.8% of 1472 unique ICI-treated patients. Median serum creatinine increased from 1.05 mg/dL at baseline to 3.50 mg/dL at biopsy assessment. During the AKI episode, 10 patients (83.3%) met Kidney Disease: Improving Global Outcomes (KDIGO) criteria for stage 3 AKI. All patients had pyuria, negative urine cultures, and subnephrotic proteinuria. Hematuria and peripheral eosinophilia occurred in four and two patients, respectively. All patients received corticosteroids, and none required kidney replacement therapy. Complete, partial, and absent recovery occurred in eight, two, and two patients, respectively; under the stricter baseline-relative definition, the corresponding numbers were five, five, and two. Conclusions: Biopsy-confirmed ICI-AIN was infrequently detected. Severe AKI was common, urinary findings were nonspecific, and residual renal dysfunction frequently persisted after corticosteroid treatment. Full article

(This article belongs to the Section Antibody-Based Therapeutics)

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13 pages, 1498 KB

Open AccessArticle

Computational Design and Expression of Headless Influenza Hemagglutinin Antigens Toward a Modular Universal Nanoparticle Vaccine

by Victor Ovchinnikov and Martin Karplus

Antibodies 2026, 15(4), 64; https://doi.org/10.3390/antib15040064 - 27 Jul 2026

Background: The elicitation of broadly neutralizing antibodies against conserved antigenic epitopes has been a focus of universal vaccine research. To facilitate immunofocusing on the conserved influenza hemagglutinin (HA) stalk, we designed headless trimeric antigens, initially focusing on subtypes H1, H3, and H5, and [...] Read more.

Background: The elicitation of broadly neutralizing antibodies against conserved antigenic epitopes has been a focus of universal vaccine research. To facilitate immunofocusing on the conserved influenza hemagglutinin (HA) stalk, we designed headless trimeric antigens, initially focusing on subtypes H1, H3, and H5, and subsequently expanding to eight additional HA subtypes. Results: The designs were first evaluated in silico; they were predicted to fold correctly by AlphaFold2, and remained stable in molecular dynamics simulations in isolation, as well as bound to a broadly neutralizing antibody. The antigens expressed in HEK293-derived cells in high yields, and eluted predominantly as trimers in SEC-HPLC. Future work will explore the use of mosaic nanoparticles decorated with headless antigens of various subtypes for the optimal elicitation of broadly neutralizing anti-influenza antibodies. Overall, our study advances the use of headless HA trimers as modular antigens toward a universal influenza vaccine. Full article

(This article belongs to the Section Humoral Immunity)

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27 pages, 1486 KB

Open AccessReview

Advances in Downstream Processing of Monoclonal Antibodies

by Michał Kołodziej and Dorota Antos

Antibodies 2026, 15(4), 63; https://doi.org/10.3390/antib15040063 - 24 Jul 2026

Although mAbs have great therapeutic potential, their use in medicine is currently limited by the high cost of their manufacturing. Significant developments in upstream processing technologies have caused downstream processing (DSP) to become the manufacturing cost-driver. DSP consists of a number of operations [...] Read more.

Although mAbs have great therapeutic potential, their use in medicine is currently limited by the high cost of their manufacturing. Significant developments in upstream processing technologies have caused downstream processing (DSP) to become the manufacturing cost-driver. DSP consists of a number of operations included in the capture, polishing, and formulation steps that contribute to excessive material and buffer consumption. This is particularly true for the capture and polishing steps, in which tedious and costly chromatographic operations are involved to ensure an adequate purity level of the medical product. The final formulation step also increases the burden of buffer consumption. This review focuses on those time- and material-consuming DSP operations and describes key issues and challenges related to their realization. In each of the steps, capture, polishing, and formulation, the platform processing approaches are presented as well as directions for their development. In addition, we present alternative nonchromatographic approaches that can potentially be used in the capture and polishing steps, such as precipitation or extraction. Furthermore, we describe mAb processing by crystallization, which can potentially serve as an alternative platform in both polishing and formulation steps. Full article

(This article belongs to the Section Antibody-Based Therapeutics)

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14 pages, 2999 KB

Open AccessArticle

Sera of Healthy First-Degree Relatives of SLE Patients Contain Autoantibodies to Globular Domains of C1q

by Ginka Cholakova, Alexandra Atanasova, Alexandra Kapogianni, Dobroslav Kyurkchiev, Bogdan Penev and Ivanka Tsacheva

Antibodies 2026, 15(4), 62; https://doi.org/10.3390/antib15040062 - 20 Jul 2026

Background/Objectives: The autoimmune disorder Systemic Lupus Erythematosus (SLE) is characterized by increased titers of autoantibodies with different specificities against autoantigens, including the complement proteins C1q, C3 and Factor H. SLE is characterized by chronic inflammation and tissue damage due to the secretion of [...] Read more.

Background/Objectives: The autoimmune disorder Systemic Lupus Erythematosus (SLE) is characterized by increased titers of autoantibodies with different specificities against autoantigens, including the complement proteins C1q, C3 and Factor H. SLE is characterized by chronic inflammation and tissue damage due to the secretion of pro-inflammatory molecules and a tissue deposition of immune complexes formed by autoantibodies and their target antigens. The inflammatory process in SLE is maintained by the phospholipase A2 (PLA2) enzymes generating pro-inflammatory lipid mediators. Hereditary and environmental factors trigger SLE, with increased genetic heritability in first-degree relatives of SLE patients. Methods: A cohort of 48 healthy FDRs of SLE patients was analyzed with the ELISA method for the presence of antibodies to complement proteins C1q, C3 and Factor H, with a focus on detecting autoepitopes both on immobilized and soluble C1q and its globular fragments ghA, ghB and ghC. The total serum PLA2 activity of FDRs was measured using the chromogenic substrate 4-nitro-3-octanoyloxy-benzoic acid (NOBA). Results: Only C1q, and specifically its globular domains in both an immobilized and soluble state, was targeted by antibodies in the healthy FDRs similarly to the pattern established in SLE patients. In contrast, C3 and Factor H which are known autoantigens in SLE were not found as targets for the antibodies in the analyzed FDRs. Some of the FDRs showed increased serum PLA2 activity, which correlated weakly with anti-C1q antibodies. Conclusions: C1q and its globular domains are estimated as autoantigenic molecules for binding in the analyzed FDRs of SLE patients. Full article

(This article belongs to the Special Issue Antibody and Autoantibody Specificities in Autoimmunity)

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22 pages, 4276 KB

Open AccessReview

Natural Versus Vaccine-Induced Immunity Against HPV: A Comparative Review of Antibody Response and Cancer Prevention

by Bogdan Ghilencea, Bianca Ilinca Moroianu, Ancuța-Iuliana Năstac, Ioana-Stefania Bostan, Anca Panaitescu, Claudia Mehedințu and Nicolae Gică

Antibodies 2026, 15(4), 61; https://doi.org/10.3390/antib15040061 - 13 Jul 2026

Human Papillomavirus (HPV) infection is the leading cause of cervical cancer, presenting a significant global health challenge. While natural infection is widespread, the resulting immune response is often characterized by weak, delayed, and type-specific antibody production, offering unreliable protection against reinfection. This review [...] Read more.

Human Papillomavirus (HPV) infection is the leading cause of cervical cancer, presenting a significant global health challenge. While natural infection is widespread, the resulting immune response is often characterized by weak, delayed, and type-specific antibody production, offering unreliable protection against reinfection. This review provides a comparative analysis of natural versus vaccine-induced immunity, focusing on antibody kinetics, duration of protection, and cancer prevention efficacy. A comprehensive search of the literature from the last decade was conducted using PubMed, ScienceDirect, and Web of Science. The findings demonstrate that, unlike natural immunity, which is dominated by cellular responses with often incomplete seroconversion, prophylactic vaccination induces high titers of neutralizing IgG antibodies against the L1 capsid protein. These responses are durable, with protection persisting for over a decade, and recent data support the high efficacy of single-dose regimens. Furthermore, vaccination has shown utility in reducing infection persistence in HPV-positive individuals and provides critical protection in immunocompromised groups. Consequently, vaccine-induced immunity is consistently superior to naturally acquired immunity, supporting World Health Organization recommendations for universal vaccination as the primary intervention for reducing the global burden of HPV-related malignancies. Full article

(This article belongs to the Section Humoral Immunity)

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13 pages, 984 KB

Open AccessReview

The Diagnostic and Clinical Significance of Anti-Mutated Citrullinated Vimentin Antibodies in Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Scoping Review

by Christian D’Elia, Giada Santagata, Serena Guiducci, Holger Bang, Mariangela Manfredi, Maria Infantino and Maurizio Benucci

Antibodies 2026, 15(4), 60; https://doi.org/10.3390/antib15040060 - 13 Jul 2026

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is one of the most severe extra-articular manifestations of rheumatoid arthritis (RA), requiring reliable biomarkers for early detection. This scoping review synthesized current evidence regarding the diagnostic performance and clinical associations of anti-mutated citrullinated vimentin (anti-MCV) antibodies [...] Read more.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is one of the most severe extra-articular manifestations of rheumatoid arthritis (RA), requiring reliable biomarkers for early detection. This scoping review synthesized current evidence regarding the diagnostic performance and clinical associations of anti-mutated citrullinated vimentin (anti-MCV) antibodies in patients with RA-ILD. A comprehensive literature search was conducted across PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library. Following systematic screening, two observational studies met the predefined inclusion criteria. Both included studies reported significantly higher anti-MCV positivity rates and/or serum levels in patients with RA-ILD compared with RA patients without pulmonary involvement. Specifically, one study identified an independent association between anti-MCV positivity and RA-ILD, while the other demonstrated significant correlations between anti-MCV titers and pulmonary function impairment, as well as disease activity markers. However, substantial heterogeneity was observed across the studies regarding assay platforms, positivity thresholds, and diagnostic cut-offs, which limits the direct comparability of results. While anti-MCV antibodies represent promising candidate biomarkers for RA-ILD, current evidence remains limited and is insufficient to establish definitive diagnostic, prognostic, or pathogenic significance. Consequently, larger, prospective, and multi-center studies utilizing standardized anti-MCV assay protocols are necessary to rigorously evaluate the clinical utility of these antibodies in the management of RA-ILD. Full article

(This article belongs to the Section Antibody-Based Diagnostics)

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20 pages, 13565 KB

Open AccessArticle

A Novel Anti-Cadherin-17 Monoclonal Antibody, Ca₁₇Mab-5, for Multiple Applications

by Reina Ito, Hiroyuki Suzuki, Kenichiro Ishikawa, Kazutake Yagi, Akira Ohkoshi, Yukio Katori, Mika K. Kaneko and Yukinari Kato

Antibodies 2026, 15(4), 59; https://doi.org/10.3390/antib15040059 - 10 Jul 2026

Background/Objectives: Cadherin-17 (CDH17, LI-cadherin) is a non-classical cadherin with an atypical structure and unique functions. CDH17 expression is restricted to normal intestinal epithelium. Furthermore, CDH17 functions as an oncoprotein that promotes tumor migration and invasion in colorectal, gastric, and pancreatic cancers. Therefore, CDH17 [...] Read more.

Background/Objectives: Cadherin-17 (CDH17, LI-cadherin) is a non-classical cadherin with an atypical structure and unique functions. CDH17 expression is restricted to normal intestinal epithelium. Furthermore, CDH17 functions as an oncoprotein that promotes tumor migration and invasion in colorectal, gastric, and pancreatic cancers. Therefore, CDH17 is an important diagnostic marker and therapeutic target. The CDH17-directed strategies, including monoclonal antibodies (mAbs), bispecific Abs, antibody–drug conjugates (ADCs), and chimeric antigen receptor (CAR) T cells, have been evaluated in preclinical and clinical studies. Therefore, developing mAbs that specifically recognize cell surface-expressing CDH17 is essential for advancing both tumor diagnosis and therapy. Methods: Anti-human CDH17 mAbs (named Ca₁₇Mabs) were developed by immunizing a mouse with CDH17-overexpressed cells and a high-throughput screening using flow cytometry. Results: Among Ca₁₇Mabs, a clone, Ca₁₇Mab-5 (IgG₁, κ) specifically recognized CDH17-overexpressed Chinese hamster ovary-K1 (CHO/CDH17) cells with no detectable cross-reactivity to 21 other CDHs by flow cytometry. Ca₁₇Mab-5 also detected endogenous CDH17 in human colorectal cancer cell lines, COLO201 and COLO205. The apparent dissociation constant (K_D) values of Ca₁₇Mab-5 for CHO/CDH17 and COLO205 were estimated as 1.5 × 10⁻⁸ M and 1.3 × 10⁻⁸ M, respectively. Furthermore, Ca₁₇Mab-5 detected endogenous CDH17 by Western blotting. In immunohistochemistry, Ca₁₇Mab-5 exhibited clear membranous staining in normal colon epithelium, colorectal, gastric, and pancreatic cancers. Conclusions: Ca₁₇Mab-5 is a versatile tool for detecting CDH17 and has potential for tumor diagnosis. Full article

(This article belongs to the Special Issue Therapeutic Antibodies: New Trends in Discovery, Developability and Characterization)

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13 pages, 380 KB

Open AccessArticle

Beyond the Surface: Antinuclear Antibodies in Rheumatoid Arthritis—Experiences from a Single-Center, Cross-Sectional Observational Study

by Hanna Cholerzyńska, Gabriela Kot, Łukasz Świątek and Bogna Grygiel-Górniak

Antibodies 2026, 15(4), 58; https://doi.org/10.3390/antib15040058 - 10 Jul 2026

Background: 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 [...] Read more.

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Full article

(This article belongs to the Section Antibody-Based Diagnostics)

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