Antibodies

8 pages, 230 KiB

Open AccessReview

Oral Paraneoplastic Pemphigus: A Scoping Review on Pathogenetic Mechanisms and Histo-Serological Profile

by Domenico De Falco, Sabrina Messina and Massimo Petruzzi

Antibodies 2024, 13(4), 95; https://doi.org/10.3390/antib13040095 - 22 Nov 2024

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Paraneoplastic pemphigus (PNP) is a rare autoimmune disorder associated with underlying neoplasms, predominantly Non-Hodgkin Lymphomas, affecting adults aged 45 to 70. This review analyzed 87 articles from MEDLINE/PubMed, Ovid and Scopus focusing on patients with oral manifestations of PNP, emphasizing histological and serological [...] Read more.

Paraneoplastic pemphigus (PNP) is a rare autoimmune disorder associated with underlying neoplasms, predominantly Non-Hodgkin Lymphomas, affecting adults aged 45 to 70. This review analyzed 87 articles from MEDLINE/PubMed, Ovid and Scopus focusing on patients with oral manifestations of PNP, emphasizing histological and serological aspects and discussing recent updates on pathogenetic options. Key findings revealed that PNP is often diagnosed before the neoplasm, with Follicular variant Non-Hodgkin Lymphoma and Castleman Disease being the most common associations. Histopathological analysis showed suprabasal acantholysis and inflammation, and serological tests identify a comprehensive autoantibody panel, underscoring the need for standardized diagnostic criteria and improved serological testing. Full article

12 pages, 1640 KiB

Open AccessArticle

Enhancing Tumor Immunity with IL-12 and PD-1 Blockade: A Strategy for Inducing Robust Central Memory T Cell Responses in Resistant Cancer Model

by Fentian Chen, Kexin Wu, Shiqi Lin, Jinlong Cui, Xiaoqing Chen, Zhiren Zeng, Na Yuan, Mujin Fang, Xue Liu, Yuanzhi Chen and Wenxin Luo

Antibodies 2024, 13(4), 94; https://doi.org/10.3390/antib13040094 - 20 Nov 2024

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Abstract

Background: Although immune checkpoint inhibitors (ICIs) have demonstrated efficacy in treating advanced cancers, their therapeutic success remains limited for many patients, with initial responders often experiencing resistance and relapse. Interleukin-12 (IL-12) is a powerful cytokine for antitumor immunotherapy, enhancing both lymphocyte recruitment into [...] Read more.

Background: Although immune checkpoint inhibitors (ICIs) have demonstrated efficacy in treating advanced cancers, their therapeutic success remains limited for many patients, with initial responders often experiencing resistance and relapse. Interleukin-12 (IL-12) is a powerful cytokine for antitumor immunotherapy, enhancing both lymphocyte recruitment into tumors and immune cell activation. Methods: In this study, we successfully produced mouse interleukin-12 (mIL12) through eukaryotic recombinant expression. In vivo, mIL12 exhibited significant control of tumor immunity in ICI-resistant and aggressive tumor models. Further mechanistic analysis indicated that treatment with mIL12 led to a substantial increase in tumor-infiltrating CD4⁺ T, CD8⁺ T, cDC1, and CD103⁺ cDC1 cells. Results: Our data underscore the potential of a combined therapeutic strategy involving IL-12 with PD-1 and CTLA-4 blockade to elicit a potent antitumor immune response. Notably, the co-administration of mIL12 and PD-1 blockade significantly enhanced the presence of central memory T cells (T_CM) within tumors. Conclusions: This study is the first to provide evidence that the combination of mIL12 and PD-1 blockers promotes the generation of T_CM, potentially contributing to a robust and durable antitumor effect. Full article

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

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14 pages, 2475 KiB

Open AccessArticle

Generation, Characterization, and Preclinical Studies of a Novel NKG2A-Targeted Antibody BRY805 for Cancer Immunotherapy

by Yaqiong Zhou, Yiru Wang, Jinfeng Liang, Jing Qian, Zhenhua Wu, Zhangzhao Gao, Jian Qi, Shanshan Zhu, Na Li, Yao Chen, Gang Chen, Lei Nie, Tingting Guo and Haibin Wang

Antibodies 2024, 13(4), 93; https://doi.org/10.3390/antib13040093 - 20 Nov 2024

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Abstract

Immuno-oncology has revolutionized cancer treatment, with NKG2A emerging as a novel target for immunotherapy. The blockade of NKG2A using the immune checkpoint inhibitor (ICI) monalizumab has been shown to enhance the responses of both NK cells and CD8+ T cells. However, monalizumab has [...] Read more.

Immuno-oncology has revolutionized cancer treatment, with NKG2A emerging as a novel target for immunotherapy. The blockade of NKG2A using the immune checkpoint inhibitor (ICI) monalizumab has been shown to enhance the responses of both NK cells and CD8+ T cells. However, monalizumab has demonstrated limited efficacy in in vitro cytotoxic assays and clinical trials. In our study, we discovered and characterized a novel anti-NKG2A antibody, BRY805, which exhibits high specificity for the human CD94/NKG2A heterodimer complex and does not bind to the activating NKG2C receptor. In vitro cytotoxicity assays demonstrated that BRY805 effectively activated NK92 cells and primary NK cells, thereby enhancing the cytotoxic activity of effector cells against cancer cells overexpressing HLA-E, with significantly greater efficacy compared to monalizumab. Furthermore, BRY805 exhibited synergistic antitumor activity when combined with PD-L1 monoclonal antibodies. In a mouse xenograft model, BRY805 showed superior tumor control relative to monalizumab and demonstrated a favorable safety profile in non-human primate studies. Full article

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10 pages, 325 KiB

Open AccessCommunication

High Prevalence of aCL-IgA and aβ2GPI-IgA in Drug-Free Schizophrenia Patients: Evidence of a Potential Autoimmune Link

by Samar Samoud, Imen Zamali, Fatma Korbi, Ahlem Mtiraoui, Ahlem Ben Hmid, Neila Hannachi, Yousr Galai, Hechmi Louzir and Yousri El Kissi

Antibodies 2024, 13(4), 92; https://doi.org/10.3390/antib13040092 - 15 Nov 2024

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Abstract

Background/Objectives: Schizophrenia (SZ) is a complex psychiatric disorder with increasing evidence pointing to an autoimmune component, including the presence of antiphospholipid antibodies (aPLs). This study aims to assess the prevalence of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (aβ2GPI) antibodies, particularly the IgG, IgA, [...] Read more.

Background/Objectives: Schizophrenia (SZ) is a complex psychiatric disorder with increasing evidence pointing to an autoimmune component, including the presence of antiphospholipid antibodies (aPLs). This study aims to assess the prevalence of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (aβ2GPI) antibodies, particularly the IgG, IgA, and IgM isotypes, in drug-free SZ patients compared to healthy controls, and explore their possible involvement in the disease’s pathophysiology. Methods: Eighty SZ patients meeting DSM-IV criteria were recruited, along with 80 matched healthy controls. Serum samples were analyzed using enzyme-linked immunosorbent assays (ELISA) to quantify IgG, IgA, and IgM isotypes of aCL and aβ2GPI. Results: SZ patients exhibited significantly higher levels of aCL-IgM and aCL-IgA (p < 0.05), as well as elevated aβ2GPI-IgA (22.5%, p < 0.001), compared to controls. No significant differences were observed in the aCL-IgG isotype. Interestingly, 72% of aPL-positive SZ patients were positive for aβ2GPI-IgA, with some also co-expressing multiple isotypes, suggesting a potential link between SZ and antiphospholipid syndrome (APS). Conclusions: This study is the first to report a high prevalence of aCL-IgA and aβ2GPI-IgA in SZ patients, highlighting a possible autoimmune involvement in the disease. The presence of multiple aPL isotypes, particularly IgA, suggests a need for further investigation into their role in SZ pathogenesis and their potential association with APS. Full article

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13 pages, 2931 KiB

Open AccessArticle

Ocular Mucous Membrane Pemphigoid Demonstrates a Distinct Autoantibody Profile from Those of Other Autoimmune Blistering Diseases: A Preliminary Study

by Yingzi Liu, Lei Bao, Dharm Sodha, Jing Li, Adrian Mansini, Ali R. Djalilian, Xiaoguang Li, Hua Qian, Norito Ishii, Takashi Hashimoto and Kyle T. Amber

Antibodies 2024, 13(4), 91; https://doi.org/10.3390/antib13040091 - 14 Nov 2024

Viewed by 386

Abstract

Background: Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of autoimmune blistering disease (AIBD), which can result in scarring and vision loss. The diagnosis of oMMP is challenging as patients often have undetectable levels of circulating autoantibodies by conventional assays. [...] Read more.

Background: Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of autoimmune blistering disease (AIBD), which can result in scarring and vision loss. The diagnosis of oMMP is challenging as patients often have undetectable levels of circulating autoantibodies by conventional assays. Likewise, the principal autoantigen in oMMP has been an area of debate. Methods: In this preliminary experiment, we performed Phage Immunoprecipitation Sequencing (PhIP-seq) on sera from patients with oMMP, as well as non-ocular MMP, bullous pemphigoid, and mucocutaneous-type pemphigus vulgaris. Results: We identified several autoantigens unique to oMMP relative to other AIBDs. We then cross-referenced these antigens against previously published single-nuclei datasets, as well as the International Mouse Phenotyping Consortium Database. Several protein hits identified in our study demonstrated enriched expression on the anterior surface epithelia, including TNKS1BP1, SEC16B, FNBP4, CASZ1, GOLGB1, DOT1L, PRDM 15, LARP4B, and RPL6. Likewise, a previous study of mouse knockout models of murine analogs CASZ1, HIP1, and ELOA2 reported that these mice showed abnormalities in terms of the ocular surface and development in the eyes. Notably, PhIP-seq failed to identify the canonical markers of AIBDs such as BP180, BP230, desmogleins 1 and 3, or integrin β4, indicating that the patient autoantibodies react with conformational epitopes rather than linear epitopes. Conclusions: oMMP patients demonstrate a unique autoantibody repertoire relative to the other AIBDs. Further validation of the identified autoantibodies will shed light on their potentially pathogenic role. Full article

(This article belongs to the Section Humoral Immunity)

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25 pages, 3686 KiB

Open AccessReview

A Brief Chronicle of Antibody Research and Technological Advances

by Kazutaka Araki and Ryota Maeda

Antibodies 2024, 13(4), 90; https://doi.org/10.3390/antib13040090 - 11 Nov 2024

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Abstract

This review briefly traces the historical development of antibody research and related technologies. The path from early perceptions of immunity to the emergence of modern immunotherapy has been marked by pivotal discoveries and technological advances. Early insights into immunity led to the development [...] Read more.

This review briefly traces the historical development of antibody research and related technologies. The path from early perceptions of immunity to the emergence of modern immunotherapy has been marked by pivotal discoveries and technological advances. Early insights into immunity led to the development of vaccination and serotherapy. The elucidation of antibody structure and function paved the way for monoclonal antibody technology and its application in diagnosis and therapy. Breakthroughs in genetic engineering have enabled the production of humanized antibodies and the advances in Fc engineering, thereby increasing therapeutic efficacy. The discovery of immune checkpoints and cytokines revolutionized the treatment of cancer and autoimmune diseases. The field continues to evolve rapidly with the advent of antibody–drug conjugates, bispecific antibodies, and CAR T-cell therapies. As we face global health challenges, antibody research remains at the forefront of medical innovation and offers promising solutions for the future. Full article

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

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18 pages, 3531 KiB

Open AccessArticle

Comparison of Conjugates Obtained Using DMSO and DMF as Solvents in the Production of Polyclonal Antibodies and ELISA Development: A Case Study on Bisphenol A

by Anna N. Berlina, Nadezhda S. Komova, Kseniya V. Serebrennikova, Anatoly V. Zherdev and Boris B. Dzantiev

Antibodies 2024, 13(4), 89; https://doi.org/10.3390/antib13040089 - 29 Oct 2024

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Abstract

When developing immunochemical test systems, it is necessary to obtain specific antibodies. Their quality depends, among other things, on the immunogen used. When preparing hapten–protein conjugates to obtain antibodies for low-molecular-weight compounds, the key factors are the structure of the hapten itself, the [...] Read more.

When developing immunochemical test systems, it is necessary to obtain specific antibodies. Their quality depends, among other things, on the immunogen used. When preparing hapten–protein conjugates to obtain antibodies for low-molecular-weight compounds, the key factors are the structure of the hapten itself, the presence of a spacer, the size of the carrier protein and the degree of its modification by hapten molecules. This work shows that one additional factor—the conditions for obtaining the hapten–protein conjugate—is overlooked. In this work, we have synthesized conjugates of bisphenol A derivative 4,4-bis(hydroxyphenyl)valeric acid (BVA), the protein carrier soybean trypsin inhibitor (STI), and bovine serum albumin (BSA) in reaction media combining water with two organic solvents: dimethylformamide (DMF) or dimethyl sulfoxide (DMSO). Namely, BSA_DMF–BVA, STI_DMF–BVA, BSA_DMSO–BVA and STI_DMSO–BVA conjugates were obtained. Rabbit polyclonal antibodies against the BSA_DMF–BVA conjugate demonstrated basically different interactions in the developed ELISA systems using either STI_DMF–BVA or STI_DMSO–BVA conjugates. The use of the STI_DMF–BVA conjugate demonstrated the absence of competition in combination with antisera obtained from BSA_DMF–BVA in an ELISA. A competitive interaction was observed only with the use of the STI_DMSO–BVA conjugate. Under the selected conditions, the detection limit of bisphenol A was 8.3 ng/mL, and the working range of determined concentrations was 18.5–290.3 ng/mL. The obtained data demonstrate the possibility of achieving sensitive immunoassays by simply varying the reaction media for the hapten–protein conjugation, which could provide an additional tool in the development of immunoassays for other low-molecular-weight compounds. Full article

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

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14 pages, 737 KiB

Open AccessReview

Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions

by Kinsley Wang and Robert Hsu

Antibodies 2024, 13(4), 88; https://doi.org/10.3390/antib13040088 - 18 Oct 2024

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Abstract

Background/Objectives: Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally, though advances in targeted therapies have improved treatment outcomes. The mesenchymal–epithelial transition (MET) gene plays a significant role in NSCLC, often through protein overexpression, exon 14 skipping mutations, [...] Read more.

Background/Objectives: Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally, though advances in targeted therapies have improved treatment outcomes. The mesenchymal–epithelial transition (MET) gene plays a significant role in NSCLC, often through protein overexpression, exon 14 skipping mutations, and gene amplification, many of which arise as resistance mechanisms to other oncogenic drivers like epidermal growth factor receptor (EGFR) mutations. This review examines the development and clinical efficacy of anti-MET antibody therapies. Methods: A comprehensive literature search was conducted using major medical databases looking at key relevant studies on anti-MET antibody studies. Both authors reviewed the literature, assessed study quality, and interpreted the results from each study. Results: Amivantamab, a bispecific EGFR/MET antibody was approved to treat EGFR exon 20 insertion and now has recently been extended to target classical EGFR mutations with progression on osimertinib. Other important anti-MET targeted therapies in development include antibody drug conjugates such as telisotuzumab vedotin, REGN5093-M114, and AZD9592 and emibetuzumab, which is a humanized immunoglobulin G4 monoclonal bivalent MET antibody. Conclusions: MET plays a significant role in NSCLC and amivantamab along with other anti-MET targeted therapies play a role in directly targeting MET and addressing acquired resistance to oncogenic drivers. Future research should focus on developing novel MET antibody drugs and exploring new therapeutic combinations to enhance treatment efficacy and overcome resistance in NSCLC. Refining biomarker-driven approaches to ensure precise patient selection is also critical to optimizing treatment outcomes. Full article

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

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11 pages, 865 KiB

Open AccessArticle

Limited Biomarker Potential for IgG Autoantibodies Reactive to Linear Epitopes in Systemic Lupus Erythematosus or Spondyloarthropathy

by S. Janna Bashar, Zihao Zheng, Aisha M. Mergaert, Ryan R. Adyniec, Srishti Gupta, Maya F. Amjadi, Sara S. McCoy, Michael A. Newton and Miriam A. Shelef

Antibodies 2024, 13(4), 87; https://doi.org/10.3390/antib13040087 - 12 Oct 2024

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Abstract

Background: Autoantibodies are commonly used as biomarkers in autoimmune diseases, but there are limitations. For example, autoantibody biomarkers have poor sensitivity or specificity in systemic lupus erythematosus and do not exist in the spondyloarthropathies, impairing diagnosis and treatment. While autoantibodies suitable for strong [...] Read more.

Background: Autoantibodies are commonly used as biomarkers in autoimmune diseases, but there are limitations. For example, autoantibody biomarkers have poor sensitivity or specificity in systemic lupus erythematosus and do not exist in the spondyloarthropathies, impairing diagnosis and treatment. While autoantibodies suitable for strong biomarkers may not exist in these conditions, another possibility is that technology has limited their discovery. The purpose of this study was to use a novel high-density peptide array that enables the evaluation of IgG binding to every possible linear antigen in the entire human peptidome, as well as a novel machine learning approach that incorporates ELISA validation predictability in order to discover autoantibodies that could be developed into sensitive and specific markers of lupus or spondyloarthropathy. Methods: We used a peptide array containing the human peptidome, several viral peptidomes, and key post-translational modifications (6 million peptides) to quantify IgG binding in lupus, spondyloarthropathy, rheumatoid arthritis, Sjögren’s disease, and control sera. Using ELISA data for 70 peptides, we performed a random forest analysis that evaluated multiple array features to predict which peptides might be good biomarkers, as confirmed by ELISA. We validated the peptide prediction methodology in rheumatoid arthritis and COVID-19, conditions for which the antibody repertoire is well-understood, and then evaluated IgG binding by ELISA to peptides that we predicted would be highly bound specifically in lupus or spondyloarthropathy. Results: Our methodology performed well in validation studies, but peptides predicted to be highly and specifically bound in lupus or spondyloarthropathy could not be confirmed by ELISA. Conclusions: In a comprehensive evaluation of the entire human peptidome, highly sensitive and specific IgG autoantibodies were not identified in lupus or spondyloarthropathy. Thus, the pathogenesis of lupus and spondyloarthropathy may not depend upon unique autoantigens, and other types of molecules should be sought as optimal biomarkers in these conditions. Full article

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

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26 pages, 419 KiB

Open AccessReview

Ophthalmic Use of Targeted Biologics in the Management of Intraocular Diseases: Current and Emerging Therapies

by Yuan Zong, Miki Miyagaki, Mingming Yang, Jing Zhang, Yaru Zou, Kyoko Ohno-Matsui and Koju Kamoi

Antibodies 2024, 13(4), 86; https://doi.org/10.3390/antib13040086 - 11 Oct 2024

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Abstract

Background: Monoclonal antibodies (mAbs) have demonstrated substantial potential in the treatment of intraocular diseases. This review aimed to comprehensively evaluate the applications, efficacy, and safety of mAbs in the management of intraocular conditions. Methods: A comprehensive literature search was conducted in major medical [...] Read more.

Background: Monoclonal antibodies (mAbs) have demonstrated substantial potential in the treatment of intraocular diseases. This review aimed to comprehensively evaluate the applications, efficacy, and safety of mAbs in the management of intraocular conditions. Methods: A comprehensive literature search was conducted in major medical databases through July 2024. Relevant studies on monoclonal antibodies for intraocular diseases were included. Two independent researchers screened the literature, extracted data, and assessed study quality. Cost-effectiveness analyses were also reviewed. Results: Anti-vascular endothelial growth factor (VEGF) antibodies, such as bevacizumab, ranibizumab, and aflibercept, showed significant therapeutic effects in neovascular age-related macular degeneration (NVAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Tumor necrosis factor-alpha (TNF-α) inhibitors demonstrated promising results in treating noninfectious uveitis. Complement system-targeted therapies like pegcetacoplan offered new options for geographic atrophy. Anti-VEGF antibodies showed potential in managing retinopathy of prematurity (ROP). However, challenges persist, including high costs, potential drug resistance, and limited long-term safety data in certain scenarios. Conclusions: Monoclonal antibodies are vital for treating intraocular diseases, but continuous innovation and rigorous clinical evaluation are essential. Future research should focus on developing novel delivery systems, exploring combination therapies, conducting long-term follow-up studies, and investigating personalized treatment strategies to provide safer, more effective, and cost-effective therapeutic solutions. Full article

20 pages, 2740 KiB

Open AccessArticle

Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector Functions

by Michelle L. McKeague, Jason Lohmueller, Matthew T. Dracz, Najla Saadallah, Eric D. Ricci, Donella M. Beckwith, Ramya Ayyalasomayajula, Maré Cudic and Olivera J. Finn

Antibodies 2024, 13(4), 85; https://doi.org/10.3390/antib13040085 - 10 Oct 2024

Viewed by 986

Abstract

Background/Objectives: Mucin-1 (MUC1) is a transmembrane glycoprotein that is overexpressed and hypoglycosylated in premalignant and malignant epithelial cells compared to normal cells, creating a target antigen for humoral and cellular immunity. Healthy individuals with a history of advanced colonic adenomas and at high [...] Read more.

Background/Objectives: Mucin-1 (MUC1) is a transmembrane glycoprotein that is overexpressed and hypoglycosylated in premalignant and malignant epithelial cells compared to normal cells, creating a target antigen for humoral and cellular immunity. Healthy individuals with a history of advanced colonic adenomas and at high risk for colon cancer were enrolled in a clinical trial to evaluate the feasibility of using a MUC1 peptide vaccine to prevent colon cancer. Anti-MUC1 antibodies elicited by this vaccine were cloned using peripheral blood B cells and sera collected two weeks after a one-year booster. Twelve of these fully human monoclonal antibodies (mAb) were tested for binding to MUC1+ target cells, and three with the highest binding were further evaluated for various effector functions important for tumor rejection. Methods: Immune cells were incubated together with target cells expressing variations in the number, distance, and membrane anchoring properties of the MUC1 epitope in the presence of each mAb. Results: All three mAbs mediated antibody-dependent cytokine release (ADCR), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). Two also mediated antibody-dependent trogocytosis/trogoptosis (ADCT). None were capable of complement-dependent cytotoxicity (CDC). Conclusions: ADCP and ADCT functions were more efficient when antibodies bound epitopes proximal to and anchored to the membrane, providing insight for future therapeutic antibody validation strategies. Full article

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

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23 pages, 2395 KiB

Open AccessReview

B Cell and Antibody Responses in Bovine Tuberculosis

by Laura Inés Klepp, Federico Carlos Blanco, María Mercedes Bigi, Cristina Lourdes Vázquez, Elizabeth Andrea García, Julia Sabio y García and Fabiana Bigi

Antibodies 2024, 13(4), 84; https://doi.org/10.3390/antib13040084 - 9 Oct 2024

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Abstract

The development of vaccines and effective diagnostic methods for bovine tuberculosis requires an understanding of the immune response against its causative agent, Mycobacterium bovis. Although this disease is primarily investigated and diagnosed through the assessment of cell-mediated immunity, the role of B [...] Read more.

The development of vaccines and effective diagnostic methods for bovine tuberculosis requires an understanding of the immune response against its causative agent, Mycobacterium bovis. Although this disease is primarily investigated and diagnosed through the assessment of cell-mediated immunity, the role of B cells and antibodies in bovine tuberculosis has been relatively undervalued and understudied. Current evidence indicates that circulating M. bovis-specific antibodies are not effective in controlling the disease. However, local humoral immune responses may contribute to either defence or pathology. Recent studies in animal models and cattle vaccine trials suggest a potential beneficial role of B cells in tuberculosis control. This review discusses the role of B cells and antibodies in bovine tuberculosis and explores antibody-based diagnostics for the disease, including traditional techniques, such as different ELISA, new platforms based on multiple antigens and point-of-care technologies. The high specificity and sensitivity values achieved by numerous antibody-based tests support their use as complementary tests for the diagnosis of bovine tuberculosis, especially for identifying infected animals that may be missed by the official tests. Full article

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15 pages, 6375 KiB

Open AccessArticle

Metabolic Engineering of Glycofusion Bispecific Antibodies for α-Dystroglycanopathies

by Xiaotian Zhong, Guoying Grace Yan, Apurva Chaturvedi, Xiuling Li, Yijie Gao, Mahasweta Girgenrath, Chris J. Corcoran, Liz Diblasio-Smith, Edward R. LaVallie, Teresse de Rham, Jing Zhou, Molica Abel, Logan Riegel, Sean K.H. Lim, Laird Bloom, Laura Lin and Aaron M. D’Antona

Antibodies 2024, 13(4), 83; https://doi.org/10.3390/antib13040083 - 7 Oct 2024

Viewed by 1237

Abstract

Background: α-dystroglycanopathies are congenital muscular dystrophies in which genetic mutations cause the decrease or absence of a unique and complex O-linked glycan called matriglycan. This hypoglycosylation of O-linked matriglycan on the α-dystroglycan (α-DG) protein subunit abolishes or reduces the protein binding to extracellular [...] Read more.

Background: α-dystroglycanopathies are congenital muscular dystrophies in which genetic mutations cause the decrease or absence of a unique and complex O-linked glycan called matriglycan. This hypoglycosylation of O-linked matriglycan on the α-dystroglycan (α-DG) protein subunit abolishes or reduces the protein binding to extracellular ligands such as laminins in skeletal muscles, leading to compromised survival of muscle cells after contraction. Methods: Surrogate molecular linkers reconnecting laminin-211 and the dystroglycan β-subunit through bispecific antibodies can be engineered to improve muscle function in the α-dystroglycanopathies. This study reports the metabolic engineering of a novel glycofusion bispecific (GBi) antibody that fuses the mucin-like domain of the α-DG to the light chain of an anti-β-DG subunit antibody. Results: Transient HEK production with the co-transfection of LARGE1, the glycoenzyme responsible for the matriglycan modification, produced the GBi antibody only with a light matriglycan modification and a weak laminin-211 binding activity. However, when a sugar feed mixture of uridine, galactose, and manganese ion (Mn²⁺) was added to the culture medium, the GBi antibody produced exhibited a dramatically enhanced matriglycan modification and a much stronger laminin-binding activity. Conclusions: Further investigation has revealed that Mn²⁺ in the sugar feeds played a critical role in increasing the matriglycan modification of the GBi antibody, key for the function of the resulting bispecific antibody. Full article

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

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12 pages, 3097 KiB

Open AccessArticle

Development of a Mammalian Cell Line for Stable Production of Anti-PD-1

by Erika Csató-Kovács, Pál Salamon, Szilvia Fikó-Lászlo, Krisztina Kovács, Alice Koka, Mónika András-Korodi, Emőke Antal, Emília Brumă, Brigitta Tőrsők, Szilárd Gudor, Ildikó Miklóssy, Kálmán Csongor Orbán, Csilla Albert, Emese Éva Bálint and Beáta Albert

Antibodies 2024, 13(4), 82; https://doi.org/10.3390/antib13040082 - 3 Oct 2024

Viewed by 1141

Abstract

Background/Objectives: Immune checkpoint blockade, particularly targeting the programmed cell death 1 (PD-1) receptor, is a promising strategy in cancer immunotherapy. The interaction between PD-1 and its ligands, PD-L1 and PD-L2, is crucial in immune evasion by tumors. Blocking this interaction with monoclonal antibodies [...] Read more.

Background/Objectives: Immune checkpoint blockade, particularly targeting the programmed cell death 1 (PD-1) receptor, is a promising strategy in cancer immunotherapy. The interaction between PD-1 and its ligands, PD-L1 and PD-L2, is crucial in immune evasion by tumors. Blocking this interaction with monoclonal antibodies like Nivolumab can restore anti-tumor immunity. This study aims to develop a stable expression system for Nivolumab-based anti-PD-1 in the Chinese Hamster Ovary (CHO) DG44 cell line using two different expression vector systems with various signal sequences. Methods: The heavy chain (HC) and light chain (LC) of Nivolumab were cloned into two expression vectors, pOptiVEC and pcDNA3.3. Each vector was engineered with two distinct signal sequences, resulting in the creation of eight recombinant plasmids. These plasmids were co-transfected into CHO DG44 cells in different combinations, allowing for the assessment of stable antibody production. Results: Both pOptiVEC and pcDNA3.3 vectors were successful in stably integrating and expressing the Nivolumab-based anti-PD-1 antibody in CHO DG44 cells. This study found that the choice of signal sequence significantly influenced the quantity of antibodies produced. The optimization of production conditions further enhanced antibody yield, indicating the potential for large-scale production. Conclusions: This study demonstrates that both pOptiVEC and pcDNA3.3 expression systems are effective for the stable production of Nivolumab-based anti-PD-1 in CHO DG44 cells. Signal sequences play a critical role in determining the expression levels, and optimizing production conditions can further increase antibody yield, supporting future applications in cancer immunotherapy. Full article

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8 pages, 1099 KiB

Open AccessArticle

Measurement of the Memory B Cell Response via Antibodies from Activated Cells

by Caroline Rockstroh, Katja Hintz, Judith Kannenberg and Christian Jassoy

Antibodies 2024, 13(4), 81; https://doi.org/10.3390/antib13040081 - 3 Oct 2024

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Abstract

Background/Objectives: The body’s immune response to infections and vaccination leads to the formation of memory B cells (MBCs), which protect against future infections. MBCs circulate in the blood, and the strength of the MBC response is measured with different tests. In this study, [...] Read more.

Background/Objectives: The body’s immune response to infections and vaccination leads to the formation of memory B cells (MBCs), which protect against future infections. MBCs circulate in the blood, and the strength of the MBC response is measured with different tests. In this study, tests to measure the MBC response were compared. Methods: An MBC enzyme-linked immunospot assay (MBC-ELISpot), which counts the antibody-releasing cells (MASCs) that arise from memory B cells in vitro, and two versions of an MBC enzyme-linked immunosorbent assay (MBC-ELISA), which measures the concentration of antibodies released by the MASCs, were compared. The lower measurement limit of MBC-ELISpot and ELISA was determined, and it was investigated how the measurement results of individual samples and in a sample of test persons correlate. Results: Both methods had similar lower limits of detection, and the antibody concentration correlated strongly with the number of MASCs in individual samples. The antibody concentrations measured on a sample correlated with Pearson correlation coefficients of R = 0.83–0.87 with the number of MASCs, and the proportion of antigen-specific antibodies in total IgG correlated with R = 0.74–0.82 with the proportion of antigen-specific MASCs in all antibody-secreting cells. Conclusions: Since the measurement sensitivity of MBC-ELISA and MBC-ELISpot is similar and the measurement results correlate strongly in a random sample, the tests are interchangeable. The MBC-ELISA has an advantage over the ELISpot in that the antibody measurements can be divided up over time, repeated, and extended. This creates new possibilities for measuring the MBC response. Full article

(This article belongs to the Section Humoral Immunity)

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19 pages, 781 KiB

Open AccessSystematic Review

Insights from Clinical Trials: Evidence-Based Recommendations for Induction Treatment of Newly Diagnosed Transplant-Eligible Multiple Myeloma

by Olga Lytvynova, Jenna Jwayyed, Daniel Pastel, Rohan Prasad, Jack Khouri, Louis Williams, Sandra Mazzoni, Shahzad Raza and Faiz Anwer

Antibodies 2024, 13(4), 80; https://doi.org/10.3390/antib13040080 - 29 Sep 2024

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Abstract

Multiple myeloma (MM) is a hematological malignancy and poses significant therapeutic challenges. This review synthesizes evidence from pivotal clinical trials to guide induction treatment for transplant-eligible (TE), newly diagnosed MM (NDMM) patients. Emphasizing the evolution from three-drug to four-drug induction therapies, we highlight [...] Read more.

Multiple myeloma (MM) is a hematological malignancy and poses significant therapeutic challenges. This review synthesizes evidence from pivotal clinical trials to guide induction treatment for transplant-eligible (TE), newly diagnosed MM (NDMM) patients. Emphasizing the evolution from three-drug to four-drug induction therapies, we highlight the integration of monoclonal antibodies, particularly CD38 recombinant monoclonal antibody agents, into treatment regimens. This analysis includes a comprehensive literature review of research from major databases and conferences conducted between 2010 and 2023, culminating in the detailed evaluation of 47 studies. The findings underscore the superiority of quadruple regimens in TE NDMM, notably those incorporating daratumumab, in achieving superior responses including progression-free survival (PFS), minimal residual disease (MRD) negativity, objective response rate (ORR), and overall survival (OS) when compared to triple-drug regimens. As treatment regimens evolve with additional agents, the improved outcomes with treatment-related adverse events should be carefully balanced. This review advocates for a paradigm shift towards quadruple induction therapies for TE NDMM, offers a detailed insight into the current landscape of MM treatment, and reinforces a new standard of care. Full article

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Open AccessReview

Unveiling GFAP Astrocytopathy: Insights from Case Studies and a Comprehensive Review of the Literature

by Panagiotis Gklinos, Fotios Athanasopoulos, Vagia Giatrakou, Nikolaos-Achilleas Arkoudis, Dorothea Pournara, Eirini Giagkou, Argyro Tountopoulou, Sofia Vassilopoulou and Dimos-Dimitrios Mitsikostas

Antibodies 2024, 13(4), 79; https://doi.org/10.3390/antib13040079 - 25 Sep 2024

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Abstract

Background: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy, which was first identified in 2016, is an immune-mediated inflammatory disorder of the nervous system characterized by antibodies targeting GFAP. The exact pathogenic mechanisms, as well as the role of anti-GFAP antibodies, remain unclear; however, [...] Read more.

Background: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy, which was first identified in 2016, is an immune-mediated inflammatory disorder of the nervous system characterized by antibodies targeting GFAP. The exact pathogenic mechanisms, as well as the role of anti-GFAP antibodies, remain unclear; however, it seems that neuroinflammation is mediated by specific CD8+ T-cells and that neoplasms or viral infections can act as the initial trigger. Although the clinical spectrum of the disease is broad and heterogenous, GFAP astrocytopathy most commonly presents as meningoencephalitis with or without myelitis. Other symptoms include headache, visual disturbances, extrapyramidal or brainstem syndromes, and psychiatric manifestations including psychosis. The disease has a characteristically favorable response to steroid treatment while relapses occur in approximately 20–30% of the patients. Methods: We present two cases of GFAP astrocytopathy admitted to our hospital: a 43-year-old male with persistent headache and a 59-year-old female with acute dysarthria and swallowing difficulties followed by cognitive and behavioral symptoms. Results: Additionally, we conduct a comprehensive review of the literature to elucidate the role of anti-GFAP antibodies in disease pathogenesis and examine imaging characteristics, clinical manifestations, and treatment options for this recently described neuroimmunological condition. Conclusions: This review presents two unusual cases of GFAP-astrocytopathy and provides evidence for the pathogenesis, clinical presentation, imaging characteristics and treatment options of the disease. Full article

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Antibodies, Volume 13, Issue 4 (December 2024) – 17 articles

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