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Targeting Neoantigens in Cancer: Possibilities and Opportunities in Breast Cancer
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Enhanced Characterization of Lysine-Linked Antibody Drug Conjugates Enabled by Middle-Down Mass Spectrometry and Higher-Energy Collisional Dissociation-Triggered Electron-Transfer/Higher-Energy Collisional Dissociation and Ultraviolet Photodissociation
Journal Description
Antibodies
Antibodies
is an international, peer-reviewed, open access journal on immunoglobulins, published quarterly 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 (Drug Discovery)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 23 days after submission; acceptance to publication is undertaken in 6.6 days (median values for papers published in this journal in the first half of 2024).
- 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.
Impact Factor:
3.0 (2023);
5-Year Impact Factor:
4.7 (2023)
Latest Articles
Enhanced N-Glycan Profiling of Therapeutic Monoclonal Antibodies through the Application of Upper-Hinge Middle-Up Level LC-HRMS Analysis
Antibodies 2024, 13(3), 66; https://doi.org/10.3390/antib13030066 - 6 Aug 2024
Abstract
Therapeutic monoclonal antibodies (mAbs) are crucial in modern medicine due to their effectiveness in treating various diseases. However, the structural complexity of mAbs, particularly their glycosylation patterns, presents challenges for quality control and biosimilarity assessment. This study explores the use of upper-hinge middle-up
[...] Read more.
Therapeutic monoclonal antibodies (mAbs) are crucial in modern medicine due to their effectiveness in treating various diseases. However, the structural complexity of mAbs, particularly their glycosylation patterns, presents challenges for quality control and biosimilarity assessment. This study explores the use of upper-hinge middle-up (UHMU)-level ultra-high-performance liquid chromatography–high-resolution mass spectrometry (LC-HRMS) analysis to improve N-glycan profiling of mAbs. Two specific enzymes, known as IgG degradation enzymes (IGDEs), were used to selectively cleave therapeutic mAbs above the hinge region to separate antibody subunits for further Fc glycan analysis by means of the UHMU/LC-HRMS workflow. The complexity of the mass spectra of IGDEs-digested mAbs was significantly reduced compared to the intact MS level, enabling reliable assignment and relative quantitation of paired Fc glycoforms. The results of the UHMU/LC-HRMS analysis of nine approved therapeutics highlight the significance of this approach for in-depth glycoform profiling.
Full article
(This article belongs to the Section Antibody-Based Therapeutics)
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Open AccessArticle
The Seraph 100® Microbind Affinity Blood Filter Does Not Alter Levels of Circulating or Mucosal Antibodies in Critical COVID-19 Patients
by
Tonia L. Conner, Pooja Vir, Eric D. Laing, Ian J. Stewart, Edward Mitre and Kathleen P. Pratt
Antibodies 2024, 13(3), 65; https://doi.org/10.3390/antib13030065 - 6 Aug 2024
Abstract
PURIFY-OBS-1 is an observational study evaluating the safety and efficacy of Seraph 100® Microbind Affinity Blood Filter (Seraph 100) use for COVID-19 patients with respiratory failure admitted to the intensive care unit (ICU). The Seraph 100 is a hemoperfusion device containing heparin-coated
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PURIFY-OBS-1 is an observational study evaluating the safety and efficacy of Seraph 100® Microbind Affinity Blood Filter (Seraph 100) use for COVID-19 patients with respiratory failure admitted to the intensive care unit (ICU). The Seraph 100 is a hemoperfusion device containing heparin-coated beads that can bind to, and reduce levels of, some circulating pathogens and inflammatory molecules. This study evaluated whether treatment with the Seraph 100 affected circulating and mucosal antibody levels in critically ill COVID-19 subjects. SARS-CoV-2 anti-spike and anti-nucleocapsid IgG and IgA levels in serum were evaluated at enrollment and on days 1, 4, 7, and 28 after Seraph 100 application, while anti-spike and nucleocapsid IgG, IgA, and secretory IgA levels in tracheal aspirates were evaluated at enrollment and on days 1, 2, 3, 7, and 28. Serum samples were also collected from the pre- and post-filter lines at 1 and 4 h following Seraph 100 application to evaluate the direct impact of the filter on circulating antibody levels. Treatment with the Seraph 100 did not alter the levels of circulating or mucosal antibodies in critically ill COVID-19 subjects admitted to the ICU.
Full article
(This article belongs to the Section Humoral Immunity)
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Graphical abstract
Open AccessArticle
Prevention of Blood Incompatibility Related Hemagglutination: Blocking of Antigen A on Red Blood Cells Using In Silico Designed Recombinant Anti-A scFv
by
Saleha Hafeez and Najam Us Sahar Sadaf Zaidi
Antibodies 2024, 13(3), 64; https://doi.org/10.3390/antib13030064 - 1 Aug 2024
Abstract
Critical blood shortages plague healthcare systems, particularly in lower-income and middle-income countries. This affects patients requiring regular transfusions and creates challenges during emergencies where universal blood is vital. To address these shortages and support blood banks during emergencies, this study reports a method
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Critical blood shortages plague healthcare systems, particularly in lower-income and middle-income countries. This affects patients requiring regular transfusions and creates challenges during emergencies where universal blood is vital. To address these shortages and support blood banks during emergencies, this study reports a method for increasing the compatibility of blood group A red blood cells (RBCs) by blocking surface antigen-A using anti-A single chain fragment variable (scFv). To enhance stability, the scFv was first modified with the addition of interdomain disulfide bonds. The most effective location for this modification was found to be H44-L232 of mutant-1a scFv. ScFv was then produced from E.coli BL21(DE3) and purified using a three-step process. Purified scFvs were then used to block maximum number of antigens-A on RBCs, and it was found that only monomers were functional, while dimers formed through incorrect domain-swapping were non-functional. These antigen-blocked RBCs displayed no clumping in hemagglutination testing with incompatible blood plasma. The dissociation constant KD was found to be 0.724 μM. Antigen-blocked RBCs have the potential to be given to other blood groups during emergencies. This innovative approach could significantly increase the pool of usable blood, potentially saving countless lives.
Full article
(This article belongs to the Section Antibody Discovery and Engineering)
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Open AccessCommunication
Knowledge of the Serological Response to the Third BNT162b2 Vaccination May Influence Compliance of Healthcare Workers to Booster Dose
by
Avi Magid, Khetam Hussein, Halima Dabaja-Younis, Moran Szwarcwort-Cohen, Ronit Almog, Michal Mekel, Avi Weissman, Gila Hyams, Vardit Gepstein, Netanel A. Horowitz, Hagar Cohen Saban, Jalal Tarabeia, Michael Halberthal and Yael Shachor-Meyouhas
Antibodies 2024, 13(3), 63; https://doi.org/10.3390/antib13030063 - 1 Aug 2024
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Background: Previous studies showed that the fourth SARS-CoV-2 vaccine dose has a protective effect against infection, as well as against severe disease and death. This study aimed to examine whether knowledge of a high-level antibody after the third dose may reduce compliance to
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Background: Previous studies showed that the fourth SARS-CoV-2 vaccine dose has a protective effect against infection, as well as against severe disease and death. This study aimed to examine whether knowledge of a high-level antibody after the third dose may reduce compliance to the fourth booster dose among healthcare workers (HCWs). Methods: We conducted a prospective cohort study among HCWs vaccinated with the first three doses at Rambam Healthcare Campus, a tertiary hospital in northern Israel. Participants underwent a serological test before the fourth booster vaccine was offered to all of them, with results provided to participants. The population was divided into two groups, namely those with antibodies below 955 AU/mL and those with 955 AU/mL and higher, a cutoff found protective in a previous study. Multiple logistic regression was carried out to compare the compliance to the fourth booster between the two groups, adjusted for demographic and clinical variables. Results: After adjusting for the confounding variables, the compliance was higher in those with antibody levels below 955 AU/mL (OR = 1.41, p = 0.05, 95% CI 1.10–1.96). In addition, male sex and age of 60 years and above were also associated with higher vaccination rates (OR = 2.28, p < 0.001, 95% CI 1.64–3.17), (OR = 1.14, p = 0.043, 95% CI 1.06–1.75), respectively. Conclusions: Knowledge of the antibody status may affect compliance with the booster dose. Considering waning immunity over time, reduced compliance may affect the protection of HCWs who declined the fourth dose.
Full article
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Open AccessArticle
Novel Flow Cytometry Method Detecting Complement C1q Bound to Blood Type A/B IgG Antibody for Preventing Severe Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation
by
Tsutomu Ishizuka, Kazuhiro Iwadoh, Hiroshi Kataoka, Junichi Hoshino, Kosaku Nitta and Hideki Ishida
Antibodies 2024, 13(3), 62; https://doi.org/10.3390/antib13030062 - 1 Aug 2024
Abstract
We aimed to develop a novel method for measuring the complement-binding ability of anti-blood type antibodies (ab-Abs), the flow cytometry method for the complement C1q test (FCM-C1q) for detecting antibody-mediated rejection (AMR) caused by ab-Abs in ABO-incompatible kidney transplantation (ABOI-KTx). FCM-C1q distribution was
[...] Read more.
We aimed to develop a novel method for measuring the complement-binding ability of anti-blood type antibodies (ab-Abs), the flow cytometry method for the complement C1q test (FCM-C1q) for detecting antibody-mediated rejection (AMR) caused by ab-Abs in ABO-incompatible kidney transplantation (ABOI-KTx). FCM-C1q distribution was surveyed in 44 healthy participants and 43 dialysis patients (Cohort A). The relationship between AMR and FCM-C1q levels was examined along with ab-Ab titers by the flow cytometry method for the IgG test (FCM-IgG) in 62 ABOI-KTx patients (Cohort B). FCM-IgG and C1q levels were significantly higher in type O participants than in A/B participants in Cohort A. There were minimal differences in the distribution of FCM-IgG and C1q between dialysis and healthy participants. Sixteen cases were suspected of acute rejections (ARs) in Cohort B, of whom nine had AR clinically. One patient with severe AMR was highly suspected of hyperacute rejection along with another patient with severe AMR. Their postoperative FCM-C1q and FCM-IgG levels were elevated. Another two patients showed high FCM-IgG and C1q levels before KTx, and these levels remained low after KTx with no or mild rejection. In conclusion, our results suggest that a high positivity rate for FCM-C1q may predict moderate to severe AMR caused by ab-Abs and poor prognosis in ABOI-KTx.
Full article
(This article belongs to the Section Antibody-Based Diagnostics)
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Graphical abstract
Open AccessReview
Allogeneic HLA Humoral Immunogenicity and the Prediction of Donor-Specific HLA Antibody Development
by
Vadim Jucaud
Antibodies 2024, 13(3), 61; https://doi.org/10.3390/antib13030061 - 24 Jul 2024
Abstract
The development of de novo donor-specific HLA antibodies (dnDSAs) following solid organ transplantation is considered a major risk factor for poor long-term allograft outcomes. The prediction of dnDSA development is a boon to transplant recipients, yet the assessment of allo-HLA immunogenicity remains imprecise.
[...] Read more.
The development of de novo donor-specific HLA antibodies (dnDSAs) following solid organ transplantation is considered a major risk factor for poor long-term allograft outcomes. The prediction of dnDSA development is a boon to transplant recipients, yet the assessment of allo-HLA immunogenicity remains imprecise. Despite the recent technological advances, a comprehensive evaluation of allo-HLA immunogenicity, which includes both B and T cell allorecognition, is still warranted. Recent studies have proposed using mismatched HLA epitopes (antibody and T cell) as a prognostic biomarker for humoral alloimmunity. However, the identification of immunogenic HLA mismatches has not progressed despite significant improvements in the identification of permissible mismatches. Certainly, the prediction of dnDSA development may benefit permissible HLA mismatched organ transplantations, personalized immunosuppression, and clinical trial design. However, characteristics that go beyond the listing of mismatched HLA antibody epitopes and T cell epitopes, such as the generation of HLA T cell epitope repertoires, recipient’s HLA class II phenotype, and immunosuppressive regiments, are required for the precise assessment of allo-HLA immunogenicity.
Full article
(This article belongs to the Special Issue Review Collection on Humoral Immunity)
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Open AccessReview
Application of Monoclonal Antibodies against Naturally Occurring Bioactive Ingredients
by
Shunsuke Fujii, Takuhiro Uto, Hiroaki Hayashi, Waraporn Putalun, Seiichi Sakamoto, Hiroyuki Tanaka and Yukihiro Shoyama
Antibodies 2024, 13(3), 60; https://doi.org/10.3390/antib13030060 - 24 Jul 2024
Abstract
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Monoclonal antibodies (Mabs) are widely used in a variety of fields, including protein identification, life sciences, medicine, and natural product chemistry. This review focuses on Mabs against naturally occurring active compounds. The preparation of Mabs against various active compounds began in the 1980s,
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Monoclonal antibodies (Mabs) are widely used in a variety of fields, including protein identification, life sciences, medicine, and natural product chemistry. This review focuses on Mabs against naturally occurring active compounds. The preparation of Mabs against various active compounds began in the 1980s, and now there are fewer than 50 types. Eastern blotting, which was developed as an antibody staining method for low-molecular-weight compounds, is useful for its ability to visually represent specific components. In this method, a mixture of lower-molecular-weight compounds, particularly glycosides, are separated by thin-layer chromatography (TLC). The compounds are then transferred to a membrane by heating, followed by treatment with potassium periodate (KIO4) to open the sugar moiety of the glycoside on the membrane to form an aldehyde group. Proteins are then added to form Schiff base bonds to enable adsorption on the membrane. A Mab is bound to the glycoside moiety on the membrane and reacts with a secondary antibody to produce color. Double Eastern blotting, which enables the simultaneous coloration of two glycosides, can be used to evaluate quality and estimate pharmacological effects. An example of staining by Eastern blotting and a component search based on the results will also be presented. A Mab-associated affinity column is a method for isolating antigen molecules in a single step. However, the usefulness of the wash fractions that are not bound to the affinity column is unknown. Therefore, we designated the wash fraction the “knockout extract”. Comparing the nitric oxide (NO) production of a glycyrrhizin (GL)-knockout extract of licorice with a licorice extract revealed that the licorice extract is stronger. Therefore, the addition of GL to the GL-knockout extract of licorice increased NO production. This indicates that GL has synergic activity with the knockout extract. The GL-knockout extract of licorice inhibited high-glucose-induced epithelial–mesenchymal transition in NRK-52E cells, primarily by suppressing the Notch2 pathway. The real active constituent in licorice may be constituents other than GL, which is the causative agent of pseudohyperaldosteronism. This suggests that a GL-knockout extract of licorice may be useful for the treatment of diabetic nephritis.
Full article
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Open AccessArticle
Adverse Events of PD-1, PD-L1, CTLA-4, and LAG-3 Immune Checkpoint Inhibitors: An Analysis of the FDA Adverse Events Database
by
Connor Frey and Mahyar Etminan
Antibodies 2024, 13(3), 59; https://doi.org/10.3390/antib13030059 - 17 Jul 2024
Abstract
This study aimed to identify the 25 most prevalent adverse events (AEs) associated with FDA-approved immune checkpoint inhibitors (ICIs)—specifically, PD-1, PD-L1, CTLA-4, and LAG-3 inhibitors—using data from the FDA Adverse Events Reporting System (FAERS), a publicly available repository of reported drug adverse events,
[...] Read more.
This study aimed to identify the 25 most prevalent adverse events (AEs) associated with FDA-approved immune checkpoint inhibitors (ICIs)—specifically, PD-1, PD-L1, CTLA-4, and LAG-3 inhibitors—using data from the FDA Adverse Events Reporting System (FAERS), a publicly available repository of reported drug adverse events, and AERSMine, an open-access pharmacovigilance tool, to investigate these adverse events. For PD-1 inhibitors, the most common AEs were diarrhea, fatigue, and pyrexia, with notable instances of neutropenia and hypothyroidism, particularly with toripalimab and dostarlimab. PD-L1 inhibitors also frequently caused pyrexia, diarrhea, and fatigue, with interstitial lung disease and hypothyroidism showing a class effect, and drug-specific AEs such as hepatotoxicity and chills. CTLA-4 inhibitors predominantly resulted in diarrhea and colitis, with ipilimumab frequently causing pyrexia and rash, while tremelimumab exhibited unique AEs such as biliary tract infection. The LAG-3 inhibitor relatlimab reported fewer AEs, including pyrexia and pneumonia. Rare but significant AEs across all inhibitors included myocarditis and myasthenia gravis. This study provides a detailed overview of the 25 most common AEs associated with ICIs, offering valuable insights for clinical decision-making and AE management. Further research is necessary to elucidate the mechanisms underlying these AEs and to develop targeted interventions to enhance the safety and efficacy of ICI therapy in patients with cancer.
Full article
(This article belongs to the Section Antibody-Based Therapeutics)
Open AccessReview
A Comparison of Natural and Therapeutic Anti-IgE Antibodies
by
Monique Vogel and Paul Engeroff
Antibodies 2024, 13(3), 58; https://doi.org/10.3390/antib13030058 - 16 Jul 2024
Abstract
Immunoglobulin E (IgE) plays a critical role for the immune system, fighting against parasites, toxins, and cancer. However, when it reacts to allergens without proper regulation, it can cause allergic reactions, including anaphylaxis, through a process initiated by effector cells such as basophils
[...] Read more.
Immunoglobulin E (IgE) plays a critical role for the immune system, fighting against parasites, toxins, and cancer. However, when it reacts to allergens without proper regulation, it can cause allergic reactions, including anaphylaxis, through a process initiated by effector cells such as basophils and mast cells. These cells display IgE on their surface, bound to the high-affinity IgE receptor FcεRI. A cross-linking antigen then triggers degranulation and the release of inflammatory mediators from the cells. Therapeutic monoclonal anti-IgE antibodies such as omalizumab, disrupt this process and are used to manage IgE-related conditions such as severe allergic asthma and chronic spontaneous urticaria. Interestingly, naturally occurring anti-IgE autoantibodies circulate at surprisingly high levels in healthy humans and mice and may thus be instrumental in regulating IgE activity. Although many open questions remain, recent studies have shed new light on their role as IgE regulators and their mechanism of action. Here, we summarize the latest insights on natural anti-IgE autoantibodies, and we compare their functional features to therapeutic monoclonal anti-IgE autoantibodies.
Full article
(This article belongs to the Special Issue Review Collection on Humoral Immunity)
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Open AccessArticle
Humanization of Pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework
by
Audrey Kassardjian, Danton Ivanochko, Brian Barber, Arif Jetha and Jean-Philippe Julien
Antibodies 2024, 13(3), 57; https://doi.org/10.3390/antib13030057 - 16 Jul 2024
Abstract
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Reducing the immunogenicity of animal-derived monoclonal antibodies (mAbs) for use in humans is critical to maximize therapeutic effectiveness and preclude potential adverse events. While traditional humanization methods have primarily focused on grafting antibody Complementarity-Determining Regions (CDRs) on homologous human antibody scaffolds, framework regions
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Reducing the immunogenicity of animal-derived monoclonal antibodies (mAbs) for use in humans is critical to maximize therapeutic effectiveness and preclude potential adverse events. While traditional humanization methods have primarily focused on grafting antibody Complementarity-Determining Regions (CDRs) on homologous human antibody scaffolds, framework regions can also play essential roles in antigen binding. Here, we describe the humanization of the pan-HLA-DR mAb 44H10, a murine antibody displaying significant involvement of the framework region in antigen binding. Using a structure-guided approach, we identify and restore framework residues that directly interact with the antigen or indirectly modulate antigen binding by shaping the antibody paratope and engineer a humanized antibody with affinity, biophysical profile, and molecular binding basis comparable to that of the parental 44H10 mAb. As a humanized molecule, this antibody holds promise as a scaffold for the development of MHC class II-targeting therapeutics and vaccines.
Full article
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Open AccessArticle
Immune-Related Adverse Events Associated with Atezolizumab: Insights from Real-World Pharmacovigilance Data
by
Connor Frey and Mahyar Etminan
Antibodies 2024, 13(3), 56; https://doi.org/10.3390/antib13030056 - 15 Jul 2024
Abstract
The advancement of immuno-oncology has brought about a significant shift in cancer treatment methods, with antibody-based immune checkpoint inhibitors like atezolizumab leading the way in this regard. However, the use of this checkpoint blockade can result in immune-related adverse events due to increased
[...] Read more.
The advancement of immuno-oncology has brought about a significant shift in cancer treatment methods, with antibody-based immune checkpoint inhibitors like atezolizumab leading the way in this regard. However, the use of this checkpoint blockade can result in immune-related adverse events due to increased T-cell activity. The full spectrum of these events is not yet completely understood. In this study, the United States FDA Adverse Event Reporting System (FAERS) was utilized to investigate immune-related adverse events linked with the use of atezolizumab. The study identified forty-nine immune-related adverse events that affected multiple organ systems, including cardiovascular, respiratory, hematologic, hepatic, renal, gastrointestinal, neurologic, musculoskeletal, dermatologic, endocrine, and systemic disorders. The strongest signals for relative risk occurred for immune-mediated encephalitis (RR = 93.443), autoimmune myocarditis (RR = 56.641), immune-mediated hepatitis (RR = 49.062), immune-mediated nephritis (RR = 40.947), and autoimmune arthritis (RR = 39.382). Despite the morbidity associated with these adverse events, emerging evidence suggests potential associations with improved survival outcomes. Overall, this report sheds light on the widespread immune-related adverse events that cause significant morbidity and mortality in patients with cancer being treated with atezolizumab and brings attention to them for the clinicians treating these patients.
Full article
(This article belongs to the Section Antibody-Based Therapeutics)
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Graphical abstract
Open AccessArticle
NK Cytotoxicity Mediated by NK-92 Cell Lines Expressing Combinations of Two Allelic Variants for FCGR3
by
Marta Freitas Monteiro, Maria Papaserafeim, Matteo Andreani, Aline Réal, Athanasios Kouklas, Daniela Reis Galvão, Jörg D. Seebach and Gisella L. Puga Yung
Antibodies 2024, 13(3), 55; https://doi.org/10.3390/antib13030055 - 12 Jul 2024
Abstract
Natural killer (NK) cells play an important role in the surveillance of viral infections and cancer. NK cell antibody-dependent cellular cytotoxicity (ADCC) and direct cytotoxicity are mediated by the recognition of antibody-coated target cells through the Fc gamma receptor IIIA (FcγRIIIa/CD16) and by
[...] Read more.
Natural killer (NK) cells play an important role in the surveillance of viral infections and cancer. NK cell antibody-dependent cellular cytotoxicity (ADCC) and direct cytotoxicity are mediated by the recognition of antibody-coated target cells through the Fc gamma receptor IIIA (FcγRIIIa/CD16) and by ligands of activating/inhibitory NK receptors, respectively. Allelic variants of the FCGR3A gene include the high-affinity single-nucleotide polymorphism (SNP) rs396991 (V176F), which is associated with the efficacy of monoclonal antibody (mAb) therapies, and the SNP rs10127939 (L66H/R). The contribution of FCGR3A SNPs to NK cell effector functions remains controversial; therefore, we generated a panel of eight NK-92 cell lines expressing specific combinations of these SNPs and tested their cytotoxicities. NK-92 cells were stably transfected with plasmids containing different combinations of FCGR3A SNPs. Messenger RNA and FcγRIIIa/CD16 cell surface expressions were detected using new generation sequencing (NGS) and flow cytometry, respectively. All FcγRIIIa/CD16-transfected NK-92 cell lines exhibited robust ADCC against three different target cell lines with minor differences. In addition, enhanced direct NK cytotoxicity against K562 target cells was observed, suggesting a mechanistic role of FcγRIIIa/CD16 in direct NK cytotoxicity. In conclusion, we generated eight FcγRIIIa/CD16-transfected NK-92 cell lines carrying different combinations of two of the most studied FCGR3A SNPs, representing the major genotypes described in the European population. The functional characterization of these cell lines revealed differences in ADCC and direct NK cytotoxicity that may have implications for the design of adoptive cancer immunotherapies using NK cells and tumor antigen-directed mAbs.
Full article
(This article belongs to the Special Issue Emerging Antibody Engineering Strategies and Applications for Immunotherapy of Cancer)
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Open AccessArticle
Inter-Antibody Variability in the Clinical Pharmacokinetics of Monoclonal Antibodies Characterized Using Population Physiologically Based Pharmacokinetic Modeling
by
Mokshada Kumar, Sravani Lanke, Alka Yadav, Mfonabasi Ette, Donald E. Mager and Dhaval K. Shah
Antibodies 2024, 13(3), 54; https://doi.org/10.3390/antib13030054 - 9 Jul 2024
Abstract
The objective of this work was to develop a population physiologically based pharmacokinetic (popPBPK) model to characterize the variability in the clinical PK of monoclonal antibodies (mAbs) following intravenous (IV) and subcutaneous (SC) administration. An extensive literature search was conducted and clinical PK
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The objective of this work was to develop a population physiologically based pharmacokinetic (popPBPK) model to characterize the variability in the clinical PK of monoclonal antibodies (mAbs) following intravenous (IV) and subcutaneous (SC) administration. An extensive literature search was conducted and clinical PK data for FDA-approved as well as non-approved mAbs were collected. Training and validation datasets of 44 and 9 mAbs exhibiting linear pharmacokinetics were used for model development. The variability in antibody PK was captured by accounting for different rate constants of pinocytosis (CLup) and intracellular degradation (kdeg) for different mAbs. Typical values for CLup and kdeg and their respective inter-antibody variabilities ( , were estimated to be 0.32 L/h/L and 26.1 (73% and 46%). Varied absorption profiles following SC dosing were characterized by incorporating inter-antibody variability in local degradation (kSC) and rate of lymphatic uptake (S_Lu) of mAbs. Estimates for typical kSC and S_Lu values, and were found to be 0.0015 and 0.54 (193%, and 49%). FDA-approved mAbs showed less local degradation (0.0014 vs. 0.0038 ) compared with other clinically tested mAbs, whereas no substantial differences in physiological processes involved in disposition were observed. To evaluate the generalizability of estimated PK parameters and model validation, the final popPBPK model was used to simulate the range of expected PK for mAbs following SC administration of nine different mAbs that were not used for model-building purposes. The predicted PK of all nine mAbs was within the expected range specified a priori. Thus, the popPBPK model presented here may serve as a tool to predict the clinical PK of mAbs with linear disposition before administering them to humans. The model may also support preclinical-to-clinical translation and ‘first-in-human’ dose determination for mAbs.
Full article
(This article belongs to the Section Antibody-Based Therapeutics)
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Open AccessCommunication
A Bead-Based Nonradioactive Immunoassay for Autoantibody Testing in a Mouse Model of Myasthenia Gravis
by
Afrin Bahauddin, Kyra Curtis, Jutatip Guptarak and Ruksana Huda
Antibodies 2024, 13(3), 53; https://doi.org/10.3390/antib13030053 - 1 Jul 2024
Abstract
Serological testing for anti-acetylcholine receptor (AChR) autoantibodies is not only crucial for the diagnosing, disease monitoring, and treatment management of patients with myasthenia gravis (MG) but also for preclinical studies utilizing MG disease models. However, there are no specific guidelines on which methods
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Serological testing for anti-acetylcholine receptor (AChR) autoantibodies is not only crucial for the diagnosing, disease monitoring, and treatment management of patients with myasthenia gravis (MG) but also for preclinical studies utilizing MG disease models. However, there are no specific guidelines on which methods to use in clinical diagnostic or research laboratories to detect or quantify any MG-specific autoantibodies. Conventional autoantibody assays, particularly those for anti-AChR antibodies, are varied and mostly laboratory-specific. Here, we report our new nonradioactive immunoprecipitation–immunoblotting method for assessing autoantibodies (anti-AChR antibodies) in a mouse model of MG. This simple, efficient, reproducible, and cost-effective assay appears superior to the enzyme-linked immunosorbent assay but comparable to the radioimmunoprecipitation or cell-based assay in specificity and sensitivity. Thus, the newly developed assay can serve as a valuable alternative to classical assays and is suitable for routine testing of AChR-specific autoantibodies in preclinical studies. The further optimization of our assay may facilitate its application in the diagnosis and therapeutic management of patients with MG.
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(This article belongs to the Section Antibody-Based Diagnostics)
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Open AccessArticle
Characterization of the Charge Heterogeneity of a Monoclonal Antibody That Binds to Both Cation Exchange and Anion Exchange Columns under the Same Binding Conditions
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Ming-Ching Hsieh, Jingming Zhang, Liangjie Tang, Cheng-Yen Huang, Yang Shen, Alice Matathia, Jun Qian and Babita Saxena Parekh
Antibodies 2024, 13(3), 52; https://doi.org/10.3390/antib13030052 - 30 Jun 2024
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Therapeutic antibodies play an important role in the public healthcare system to treat patients with a variety of diseases. Protein characterization using an array of analytical tools provides in-depth information for drug quality, safety, efficacy, and the further understanding of the molecule. A
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Therapeutic antibodies play an important role in the public healthcare system to treat patients with a variety of diseases. Protein characterization using an array of analytical tools provides in-depth information for drug quality, safety, efficacy, and the further understanding of the molecule. A therapeutic antibody candidate MAB1 exhibits unique binding properties to both cation and anion exchange columns at neutral pH. This uniqueness disrupts standard purification processes and necessitates adjustments in manufacturing. This study identifies that the charge heterogeneity of MAB1 is primarily due to the N-terminal cyclization of glutamine to pyroglutamine and, to a lesser extent, succinimide intermediate, deamidation, and C-terminal lysine. Using three approaches, i.e., deferential chemical labeling, H/D exchange, and molecular modeling, the binding to anion exchange resins is attributed to negatively charged patches on the antibody’s surface, involving specific carboxylic acid residues. The methodologies shown here can be extended to study protein binding orientation in column chromatography.
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Open AccessArticle
177Lu Anti-Angiogenic Radioimmunotherapy Targeting ATP Synthase in Gastric Cancer Model
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Bok-Nam Park, Young-Sil An, Su-Min Kim, Su-Jin Lee, Yong-Jin Park and Joon-Kee Yoon
Antibodies 2024, 13(3), 51; https://doi.org/10.3390/antib13030051 - 27 Jun 2024
Abstract
This study investigated a novel radioimmunotherapy strategy for targeting tumor angiogenesis. We developed a radiopharmaceutical complex by labeling an anti-adenosine triphosphate synthase (ATPS) monoclonal antibody (mAb) with the radioisotope 177Lu using DOTA as a chelating agent. 177Lu-DOTA-ATPS mAb demonstrated high labeling
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This study investigated a novel radioimmunotherapy strategy for targeting tumor angiogenesis. We developed a radiopharmaceutical complex by labeling an anti-adenosine triphosphate synthase (ATPS) monoclonal antibody (mAb) with the radioisotope 177Lu using DOTA as a chelating agent. 177Lu-DOTA-ATPS mAb demonstrated high labeling efficiency (99.0%) and stability in serum. MKN-45 cancer cells exhibited the highest cellular uptake, which could be specifically blocked by unlabeled ATPS mAb. In mice, 177Lu-DOTA-ATPS mAb accumulated significantly in tumors, with a tumor uptake of 16.0 ± 1.5%ID/g on day 7. 177Lu-DOTA-ATPS mAb treatment significantly reduced the viability of MKN-45 cells in a dose-dependent manner. In a xenograft tumor model, this radioimmunotherapy strategy led to substantial tumor growth inhibition (82.8%). Furthermore, combining 177Lu-DOTA-ATPS mAb with sunitinib, an anti-angiogenic drug, enhanced the therapeutic efficacy of sunitinib in the mouse model. Our study successfully developed 177Lu-DOTA-ATPS mAb, a radioimmunotherapy agent targeting tumor blood vessels. This approach demonstrates significant promise for inhibiting tumor growth, both as a single therapy and in combination with other anti-cancer drugs.
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(This article belongs to the Special Issue Emerging Antibody Engineering Strategies and Applications for Immunotherapy of Cancer)
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Open AccessArticle
Development, Optimization and Evaluation of a Sensitive Enzyme-Linked Immunosorbent Assay (ELISA) Prototype for Detection of Chicken-Based IgY Polyclonal Antibodies against Toxins of D. polylepis Venom
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Stephen Wilson Kpordze, Gideon Mutie Kikuvi, James Hungo Kimotho and Victor Atunga Mobegi
Antibodies 2024, 13(3), 50; https://doi.org/10.3390/antib13030050 - 21 Jun 2024
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Abstract
Life-threatening medical issues can result from snakebite, and hence this is a public health concern. In many tropical and subtropical nations such as Kenya, where a wide variety of poisonous snakes are prevalent, diagnosis of snakebite in health facilities is imperative. Different antivenoms
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Life-threatening medical issues can result from snakebite, and hence this is a public health concern. In many tropical and subtropical nations such as Kenya, where a wide variety of poisonous snakes are prevalent, diagnosis of snakebite in health facilities is imperative. Different antivenoms are needed to treat the venom of different snake species. Nonetheless, it might be difficult for medical professionals to identify the exact snake species that envenomated a patient due to the similarities of several snake envenomations’ clinical symptoms. Therefore, the necessity for an assay or technique for identifying venomous species is critical. The current study sought to develop a sensitive ELISA prototype for the detection of D. polylepis venom in Kenya using generated chicken-based IgY polyclonal antibodies. Serum samples containing specific chicken-based IgY antibodies previously raised against D. polylepis venom toxins were used in the assay development. ELISA parameters were optimized, and the developed assay was assessed for applicability. The limit of detection (LoD) of the ELISA for neurotoxic venoms was determined to be 0.01 µg/mL. Successful discrimination between neurotoxic and cytotoxic venoms was achieved by the ensuing inhibition ELISA assay. The developed assay showed the capability of identifying venoms in blood samples (from spiked and venom-challenged blood samples) of BALB/c mice, providing compelling evidence of the strategy’s usefulness. This assay could help physicians diagnose and manage victims of snakebites through the evaluation of clinical samples.
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(This article belongs to the Section Antibody-Based Diagnostics)
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Open AccessArticle
Screening for TORCH Antibodies in Croatian Childbearing-Aged Women, 2014–2023
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Tatjana Vilibic-Cavlek, Branko Kolaric, Marko Belamaric, Mario Sviben, Thomas Ferenc, Dan Navolan, Viktor Bekic, Ljiljana Milasincic, Ljiljana Antolasic, Maja Vilibic, Mateja Vujica Ferenc, Ema Reicher, Tadej Jezek, Ioana Ciohat, Raluca Catalina Parvanescu, Matea Kos and Maja Bogdanic
Antibodies 2024, 13(2), 49; https://doi.org/10.3390/antib13020049 - 18 Jun 2024
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TORCH infections usually result in mild maternal morbidity, but may cause severe congenital abnormalities. Therefore, it is important to detect maternal infections, monitor the fetus after the disease has been recognized, and define the seronegative women who are at risk of primary infection
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TORCH infections usually result in mild maternal morbidity, but may cause severe congenital abnormalities. Therefore, it is important to detect maternal infections, monitor the fetus after the disease has been recognized, and define the seronegative women who are at risk of primary infection during pregnancy. From 2014 to 2023, serum samples from 1032 childbearing-aged and pregnant women (16–45 years) were tested for IgM/IgG antibodies to the most common TORCH pathogens: Toxoplasma gondii, rubella virus (RUBV), cytomegalovirus (CMV), and herpes simplex viruses (HSV-1 and HSV-2). The overall IgG seroprevalence rates were 20.1% for T. gondii, 91.3% for RUBV, 70.5% for CMV, 66.8% for HSV-1, and 3.5% for HSV-2. Only HSV-2 seroprevalence was age-related, with a significant progressive increase in seropositivity from 0% in those aged less than 26 years to 9.3% in those older than 40 years. The seroprevalence of T. gondii was higher in residents of suburban/rural areas than in residents of urban areas (27.4% vs. 17.1%). In addition, participants from continental regions were more often toxoplasma-seropositive than those from coastal regions (22.2% vs. 15.3%). HSV-1 seroprevalence was also higher in suburban/rural areas (71.7% vs. 64.7%). Obstetric history was not associated with TORCH seropositivity. Univariate and multivariate risk analysis showed that suburban/rural areas of residence and continental geographic regions were significant risk factors for T. gondii seroprevalence. Furthermore, suburban/rural area of residence was a significant risk factor for HSV-1 seroprevalence, while older age was a significant risk factor for HSV-2 seroprevalence. A declining trend in the seroprevalence of all TORCH pathogens was observed compared to previous Croatian studies (2005–2011). Similarly, the proportion of women simultaneously IgG-seropositive to two or three pathogens decreased over time. The maternal serology before pregnancy could potentially reduce the burden of congenital TORCH infections.
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Open AccessArticle
Adoptive Cell Therapy in Mice Sensitized to a Grass Pollen Allergen
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Anna Marianne Weijler, Lisa Prickler, Verena Kainz, Eva Bergmann, Barbara Bohle, Heinz Regele, Rudolf Valenta, Birgit Linhart and Thomas Wekerle
Antibodies 2024, 13(2), 48; https://doi.org/10.3390/antib13020048 - 18 Jun 2024
Abstract
The proportion of patients with type I allergy in the world population has been increasing and with it the number of people suffering from allergic symptoms. Recently we showed that prophylactic cell therapy employing allergen-expressing bone marrow (BM) cells or splenic B cells
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The proportion of patients with type I allergy in the world population has been increasing and with it the number of people suffering from allergic symptoms. Recently we showed that prophylactic cell therapy employing allergen-expressing bone marrow (BM) cells or splenic B cells induced allergen-specific tolerance in naïve mice. Here we investigated if cell therapy can modulate an established secondary allergen-specific immune response in pre-immunized mice. We sensitized mice against the grass pollen allergen Phl p 5 and an unrelated control allergen, Bet v 1, from birch pollen before the transfer of Phl p 5-expressing BM cells. Mice were conditioned with several combinations of low-dose irradiation, costimulation blockade, rapamycin and T cell-depleting anti-thymocyte globulin (ATG). Levels of allergen-specific IgE and IgG1 in serum after cell transfer were measured via ELISA and alterations in cellular responses were measured via an in vitro proliferation assay and transplantation of Phl p 5+ skin grafts. None of the tested treatment protocols impacted Phl p 5-specific antibody levels. Transient low-level chimerism of Phl p 5+ leukocytes as well as a markedly prolonged skin graft survival were observed in mice conditioned with high numbers of Phl p 5+ BMC or no sensitization events between the day of cell therapy and skin grafting. The data presented herein demonstrate that a pre-existing secondary allergen-specific immune response poses a substantial hurdle opposing tolerization through cell therapy and underscore the importance of prophylactic approaches for the prevention of IgE-mediated allergy.
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(This article belongs to the Section Humoral Immunity)
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Open AccessArticle
Elevated Immunoglobulin E Serum Levels: Possible Underlying Factors That Can Cause an Inborn Error of Immunity in the Pediatric Population with Recurrent Infections
by
Sînziana Oprițescu, Gabriela Viorela Nițescu, Daniela Cîrnațu, Svetlana Trifunschi, Melania Munteanu, Mihaela Golumbeanu, Dora Boghițoiu, Adriana Maria Dărăban, Elena Iuliana Ilie and Elena Moroșan
Antibodies 2024, 13(2), 47; https://doi.org/10.3390/antib13020047 - 17 Jun 2024
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Elevated immunoglobulin E (IgE) levels are commonly associated with allergies. However, high IgE levels are also found in several other infectious and non-infectious disorders. Elevated IgE levels typically suggest allergies, eczema, or recurrent skin infections. Hyperimmunoglobulin E (hyper-IgE) levels typically reflect a monogenic
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Elevated immunoglobulin E (IgE) levels are commonly associated with allergies. However, high IgE levels are also found in several other infectious and non-infectious disorders. Elevated IgE levels typically suggest allergies, eczema, or recurrent skin infections. Hyperimmunoglobulin E (hyper-IgE) levels typically reflect a monogenic atopic condition or inborn immune defects with an atopic phenotype. The aim of our research is to investigate and observe the clinical characteristics of children with increased IgE levels who have previously manifested infectious diseases. Furthermore, the retrospective study considers other factors, such as demographic characteristics (sex, area/environment, and age), and their effect on IgE serum levels. To answer this question, we conducted a one-year hospital-based retrospective study that included 200 hospitalized children who had at least two viral or bacterial infections in the six months preceding hospitalization. Measurements of IgE and allergen panels (respiratory and digestive) using blood samples revealed that individuals who tested positive for the body’s synthesis of hyper-IgE were not observably allergic to any potential allergens despite having higher total serum IgE. According to the results, there was a strong correlation between elevated IgE serum levels and a history of infectious diseases among the patients.
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