Antibodies

11 pages, 556 KiB

Open AccessEditor’s ChoiceArticle

Investigation of Possible Factors Influencing the Neutralizing Anti-SARS-CoV-2 Antibody Titer after Six Months from the Second Vaccination Dose in a Sample of Italian Nursing Home Personnel

by Alberto Modenese, Stefania Paduano, Rossana Bellucci, Simona Marchetti, Fulvio Bruno, Pietro Grazioli, Roberto Vivoli, Fabriziomaria Gobba and Annalisa Bargellini

Antibodies 2022, 11(3), 59; https://doi.org/10.3390/antib11030059 - 19 Sep 2022

Cited by 4 | Viewed by 2350

Abstract

The titer of the anti-SARS-CoV-2 antibodies produced after vaccination shows a relevant decay over time, as demonstrated in several studies. However, less is known on the possible factors affecting the entity of this decay. The aim of this study is to analyze a [...] Read more.

The titer of the anti-SARS-CoV-2 antibodies produced after vaccination shows a relevant decay over time, as demonstrated in several studies. However, less is known on the possible factors affecting the entity of this decay. The aim of this study is to analyze a group of individual factors which are possibly associated with anti-SARS-CoV-2 antibody titer decay six months after the second vaccine dose. We report here the results of a follow-up serological analysis and a questionnaire-based evaluation of a sample of workers from an Italian nursing home, vaccinated with two doses of BNT162b2 vaccine in early 2021. The baseline data were collected one month after the vaccine, while in the present analysis we report the data collected six months later. Our data show a relevant decay of the neutralizing antibody titer, even if for all the workers a largely positive response was detected. Moreover, our results demonstrate a possible association between younger age and the absence of previous COVID-19 infection, and a higher decay rate of the anti-SARS-CoV-2 antibodies titer. Full article

(This article belongs to the Special Issue Coronavirus-Targeting Antibodies)

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43 pages, 6206 KiB

Open AccessReview

Role of HLA-I Structural Variants and the Polyreactive Antibodies They Generate in Immune Homeostasis

by Mepur H. Ravindranath, Fatiha El Hilali, Carly J. Amato-Menker, Hajar El Hilali, Senthamil R. Selvan and Edward J. Filippone

Antibodies 2022, 11(3), 58; https://doi.org/10.3390/antib11030058 - 8 Sep 2022

Cited by 2 | Viewed by 4236

Abstract

Cell-surface HLA-I molecules consisting of β2-microglobulin (β2m) associated heavy chains (HCs), referred to as Face-1, primarily present peptides to CD8+ T-cells. HCs consist of three α-domains, with selected amino acid sequences shared by all alleles of all six isoforms. The cell-surface HLA undergoes [...] Read more.

Cell-surface HLA-I molecules consisting of β2-microglobulin (β2m) associated heavy chains (HCs), referred to as Face-1, primarily present peptides to CD8+ T-cells. HCs consist of three α-domains, with selected amino acid sequences shared by all alleles of all six isoforms. The cell-surface HLA undergoes changes upon activation by pathological conditions with the expression of β2m-free HCs (Face-2) resulting in exposure of β2m-masked sequences shared by almost all alleles and the generation of HLA-polyreactive antibodies (Abs) against them. Face-2 may homodimerize or heterodimerize with the same (Face-3) or different alleles (Face-4) preventing exposure of shared epitopes. Non-allo immunized males naturally carry HLA-polyreactive Abs. The therapeutic intravenous immunoglobulin (IVIg) purified from plasma of thousands of donors contains HLA-polyreactive Abs, admixed with non-HLA Abs. Purified HLA-polyreactive monoclonal Abs (TFL-006/007) generated in mice after immunizing with Face-2 are documented to be immunoregulatory by suppressing or activating different human lymphocytes, much better than IVIg. Our objectives are (a) to elucidate the complexity of the HLA-I structural variants, and their Abs that bind to both shared and uncommon epitopes on different variants, and (b) to examine the roles of those Abs against HLA-variants in maintaining immune homeostasis. These may enable the development of personalized therapeutic strategies for various pathological conditions. Full article

(This article belongs to the Section Humoral Immunity)

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13 pages, 2187 KiB

Open AccessEditor’s ChoiceArticle

In Vitro and In Vivo Characterization of a Broadly Neutralizing Anti-SARS-CoV-2 Antibody Isolated from a Semi-Immune Phage Display Library

by Edith González-González, Gregorio Carballo-Uicab, Juana Salinas-Trujano, María I. Cortés-Paniagua, Said Vázquez-Leyva, Luis Vallejo-Castillo, Ivette Mendoza-Salazar, Keyla Gómez-Castellano, Sonia M. Pérez-Tapia and Juan C. Almagro

Antibodies 2022, 11(3), 57; https://doi.org/10.3390/antib11030057 - 6 Sep 2022

Cited by 4 | Viewed by 3164

Abstract

Neutralizing antibodies targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and/or treat COVID-19. However, as SARS-CoV-2 has evolved into new variants, most of the neutralizing antibodies authorized by the US FDA and/or EMA to treat COVID-19 [...] Read more.

Neutralizing antibodies targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and/or treat COVID-19. However, as SARS-CoV-2 has evolved into new variants, most of the neutralizing antibodies authorized by the US FDA and/or EMA to treat COVID-19 have shown reduced efficacy or have failed to neutralize the variants of concern (VOCs), particularly B.1.1.529 (Omicron). Previously, we reported the discovery and characterization of antibodies with high affinity for SARS-CoV-2 RBD Wuhan (WT), B.1.617.2 (Delta), and B.1.1.529 (Omicron) strains. One of the antibodies, called IgG-A7, also blocked the interaction of human angiotensin-converting enzyme 2 (hACE2) with the RBDs of the three strains, suggesting it may be a broadly SARS-CoV-2 neutralizing antibody. Herein, we show that IgG-A7 efficiently neutralizes all the three SARS-CoV-2 strains in plaque reduction neutralization tests (PRNTs). In addition, we demonstrate that IgG-A7 fully protects K18-hACE2 transgenic mice infected with SARS-CoV-2 WT. Taken together, our findings indicate that IgG-A7 could be a suitable candidate for development of antibody-based drugs to treat and/or prevent SARS-CoV-2 VOCs infection. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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25 pages, 1041 KiB

Open AccessEditor’s ChoiceReview

Alternative Routes of Administration for Therapeutic Antibodies—State of the Art

by Aubin Pitiot, Nathalie Heuzé-Vourc’h and Thomas Sécher

Antibodies 2022, 11(3), 56; https://doi.org/10.3390/antib11030056 - 26 Aug 2022

Cited by 22 | Viewed by 8334

Abstract

Background: For the past two decades, there has been a huge expansion in the development of therapeutic antibodies, with 6 to 10 novel entities approved each year. Around 70% of these Abs are delivered through IV injection, a mode of administration allowing rapid [...] Read more.

Background: For the past two decades, there has been a huge expansion in the development of therapeutic antibodies, with 6 to 10 novel entities approved each year. Around 70% of these Abs are delivered through IV injection, a mode of administration allowing rapid and systemic delivery of the drug. However, according to the evidence presented in the literature, beyond the reduction of invasiveness, a better efficacy can be achieved with local delivery. Consequently, efforts have been made toward the development of innovative methods of administration, and in the formulation and engineering of novel Abs to improve their therapeutic index. Objective: This review presents an overview of the routes of administration used to deliver Abs, different from the IV route, whether approved or in the clinical evaluation stage. We provide a description of the physical and biological fundamentals for each route of administration, highlighting their relevance with examples of clinically-relevant Abs, and discussing their strengths and limitations. Methods: We reviewed and analyzed the current literature, published as of the 1 April 2022 using MEDLINE and EMBASE databases, as well as the FDA and EMA websites. Ongoing trials were identified using clinicaltrials.gov. Publications and data were identified using a list of general keywords. Conclusions: Apart from the most commonly used IV route, topical delivery of Abs has shown clinical successes, improving drug bioavailability and efficacy while reducing side-effects. However, additional research is necessary to understand the consequences of biological barriers associated with local delivery for Ab partitioning, in order to optimize delivery methods and devices, and to adapt Ab formulation to local delivery. Novel modes of administration for Abs might in fine allow a better support to patients, especially in the context of chronic diseases, as well as a reduction of the treatment cost. Full article

(This article belongs to the Special Issue Women's Special Issue Series: Recent Development for Improved Therapeutic Antibodies)

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8 pages, 489 KiB

Open AccessEditor’s ChoiceReview

Mitochondrial Autoantibodies and the Role of Apoptosis in Pemphigus Vulgaris

by Dana M. Hutchison, Anna-Marie Hosking, Ellen M. Hong and Sergei A. Grando

Antibodies 2022, 11(3), 55; https://doi.org/10.3390/antib11030055 - 25 Aug 2022

Cited by 5 | Viewed by 4025

Abstract

Pemphigus vulgaris (PV) is an IgG autoantibody-mediated, potentially fatal mucocutaneous disease manifested by progressive non-healing erosions and blisters. Beyond acting to inhibit adhesion molecules, PVIgGs elicit a unique process of programmed cell death and detachment of epidermal keratinocytes termed apoptolysis. Mitochondrial damage by [...] Read more.

Pemphigus vulgaris (PV) is an IgG autoantibody-mediated, potentially fatal mucocutaneous disease manifested by progressive non-healing erosions and blisters. Beyond acting to inhibit adhesion molecules, PVIgGs elicit a unique process of programmed cell death and detachment of epidermal keratinocytes termed apoptolysis. Mitochondrial damage by antimitochondrial antibodies (AMA) has proven to be a critical link in this process. AMA act synergistically with other autoantibodies in the pathogenesis of PV. Importantly, absorption of AMA inhibits the ability of PVIgGs to induce blisters. Pharmacologic agents that protect mitochondrial function offer a new targeted approach to treating this severe immunoblistering disease. Full article

(This article belongs to the Special Issue Advances in the Use of Therapeutic Antibodies and Identification of Novel Autoantibodies in Dermatologic Disease)

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18 pages, 4071 KiB

Open AccessArticle

Anticalin N- or C-Terminal on a Monoclonal Antibody Affects Both Production and In Vitro Functionality

by Nicolas Aubrey, Valérie Gouilleux-Gruart, Christine Dhommée, Julie Mariot, Fanny Boursin, Nicolas Albrecht, Cécile Bergua, Cécile Croix, Mäelle Gilotin, Eloi Haudebourg, Catherine Horiot, Laetitia Matthias, Caroline Mouline, Laurie Lajoie, Audrey Munos, Gilles Ferry, Marie-Claude Viaud-Massuard, Gilles Thibault and Florence Velge-Roussel

Antibodies 2022, 11(3), 54; https://doi.org/10.3390/antib11030054 - 22 Aug 2022

Cited by 2 | Viewed by 3107

Abstract

Bispecific antibodies (BsAbs) represent an important advance in innovative therapeutic strategies. Among the countless formats of BsAbs, fusion with molecules such as anticalins linked to a monoclonal antibody (mAb), represents an easy and low-cost way to obtain innovative molecules. We fused an anticalin [...] Read more.

Bispecific antibodies (BsAbs) represent an important advance in innovative therapeutic strategies. Among the countless formats of BsAbs, fusion with molecules such as anticalins linked to a monoclonal antibody (mAb), represents an easy and low-cost way to obtain innovative molecules. We fused an anticalin against human fibronectin to a molecule biosimilar to trastuzumab (H0) or rituximab (R0), in four different positions, two on the N terminal region of heavy or light chains and two on the C terminal region. The eight BsAbs (H family (HF) 1 to 4 and R family (RF) 1 to 4) were produced and their affinity parameters and functional properties evaluated. The presence of anticalin did not change the glycosylation of the BsAb, shape or yield. The antigenic recognition of each BsAb family, Her2 for HF1 to 4 and CD20 for RF1 to 4, was slightly decreased (HF) or absent (RF) for the anticalin N-terminal in the light chain position. The anticalin recognition of FN was slightly decreased for the HF family, but a dramatic decrease was observed for RF members with lowest affinity for RF1. Moreover, functional properties of Abs, such as CD16 activation of NK, CD32-dependent phagocytosis and FcRn transcytosis, confirmed that this anticalin position leads to less efficient BsAbs, more so for RF than HF molecules. Nevertheless, all BsAbs demonstrated affinities for CD16, CD32 and FcRn, which suggests that more than affinity for FcRs is needed for a functioning antibody. Our strategy using anticalin and Abs allows for rapid generation of BsAbs, but as suggested by our results, some positions of anticalins on Abs result in less functionality. Full article

(This article belongs to the Special Issue Women's Special Issue Series: Recent Development for Improved Therapeutic Antibodies)

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7 pages, 1078 KiB

Open AccessArticle

Quantitation and Identification of Therapeutic Anti-CD22 Monoclonal Antibodies in a Cell-Based ELISA Method

by Shengyu Fu and Qi Zhao

Antibodies 2022, 11(3), 53; https://doi.org/10.3390/antib11030053 - 16 Aug 2022

Viewed by 3212

Abstract

Since they lack native soluble membrane antigens, the analysis and selection of antigen-specific antibodies are commonly performed on whole live cells. Here, we have developed a simple and convenient enzyme-linked immunosorbent assay (ELISA) based on cell membrane antigens. Soluble cell membrane proteins isolated [...] Read more.

Since they lack native soluble membrane antigens, the analysis and selection of antigen-specific antibodies are commonly performed on whole live cells. Here, we have developed a simple and convenient enzyme-linked immunosorbent assay (ELISA) based on cell membrane antigens. Soluble cell membrane proteins isolated from Raji cells were immobilized on the polystyrene microplate, which permitted the assessment of a therapeutic anti-CD22 monoclonal antibody. The experiments showed less variability in the intra-assay. Compared to the living cell ELISAs, the advantage of the assay is avoiding cell losses and high variation of optical density (OD) readings. We provide a quantitative and reproducible ELISA that can be potentially applied to the development of specific antibodies against cell surface antigens. Full article

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

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12 pages, 588 KiB

Open AccessEditor’s ChoiceReview

IgG Avidity Test as a Tool for Discrimination between Recent and Distant Toxoplasma gondii Infection—Current Status of Studies

by Lucyna Holec-Gąsior and Karolina Sołowińska

Antibodies 2022, 11(3), 52; https://doi.org/10.3390/antib11030052 - 15 Aug 2022

Cited by 10 | Viewed by 9233

Abstract

Toxoplasma gondii, an obligate intracellular protozoan parasite, is the causative agent of one of the most prevalent zoonoses worldwide. T. gondii infection is extremely important from a medical point of view, especially for pregnant women, newborns with congenital infections, and immunocompromised individuals. [...] Read more.

Toxoplasma gondii, an obligate intracellular protozoan parasite, is the causative agent of one of the most prevalent zoonoses worldwide. T. gondii infection is extremely important from a medical point of view, especially for pregnant women, newborns with congenital infections, and immunocompromised individuals. Thus, an accurate and proper diagnosis of this infection is essential. Among the available diagnostic tests, serology is commonly used. However, traditional serological techniques have certain limitations in evaluating the duration of T. gondii infection, which is problematic, especially for pregnant women. Avidity of T. gondii-specific IgG antibodies seems to be a significant tool for discrimination between recent and distant infections. This article describes the problem of diagnosis of T. gondii infection, with regard to IgG avidity tests. The IgG avidity test is a useful serological indicator of toxoplasmosis, which in many cases can confirm or exclude the active form of the disease. IgG antibodies produced in the recent primary T. gondii infection are of low avidity while IgG antibodies with high avidity are detected in the chronic phase of infection. Furthermore, this paper presents important topics of current research that concern the usage of parasite recombinant antigens that may improve the performance of IgG avidity tests. Full article

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

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19 pages, 2152 KiB

Open AccessEditor’s ChoiceArticle

On the Rapid Calculation of Binding Affinities for Antigen and Antibody Design and Affinity Maturation Simulations

by Simone Conti, Edmond Y. Lau and Victor Ovchinnikov

Antibodies 2022, 11(3), 51; https://doi.org/10.3390/antib11030051 - 3 Aug 2022

Cited by 6 | Viewed by 5310

Abstract

The accurate and efficient calculation of protein-protein binding affinities is an essential component in antibody and antigen design and optimization, and in computer modeling of antibody affinity maturation. Such calculations remain challenging despite advances in computer hardware and algorithms, primarily because proteins are [...] Read more.

The accurate and efficient calculation of protein-protein binding affinities is an essential component in antibody and antigen design and optimization, and in computer modeling of antibody affinity maturation. Such calculations remain challenging despite advances in computer hardware and algorithms, primarily because proteins are flexible molecules, and thus, require explicit or implicit incorporation of multiple conformational states into the computational procedure. The astronomical size of the amino acid sequence space further compounds the challenge by requiring predictions to be computed within a short time so that many sequence variants can be tested. In this study, we compare three classes of methods for antibody/antigen (Ab/Ag) binding affinity calculations: (i) a method that relies on the physical separation of the Ab/Ag complex in equilibrium molecular dynamics (MD) simulations, (ii) a collection of 18 scoring functions that act on an ensemble of structures created using homology modeling software, and (iii) methods based on the molecular mechanics-generalized Born surface area (MM-GBSA) energy decomposition, in which the individual contributions of the energy terms are scaled to optimize agreement with the experiment. When applied to a set of 49 antibody mutations in two Ab/HIV gp120 complexes, all of the methods are found to have modest accuracy, with the highest Pearson correlations reaching about 0.6. In particular, the most computationally intensive method, i.e., MD simulation, did not outperform several scoring functions. The optimized energy decomposition methods provided marginally higher accuracy, but at the expense of requiring experimental data for parametrization. Within each method class, we examined the effect of the number of independent computational replicates, i.e., modeled structures or reinitialized MD simulations, on the prediction accuracy. We suggest using about ten modeled structures for scoring methods, and about five simulation replicates for MD simulations as a rule of thumb for obtaining reasonable convergence. We anticipate that our study will be a useful resource for practitioners working to incorporate binding affinity calculations within their protein design and optimization process. Full article

(This article belongs to the Special Issue Computational Discovery of Antibodies)

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11 pages, 771 KiB

Open AccessReview

Fc-Dependent Immunomodulation Induced by Antiviral Therapeutic Antibodies: New Perspectives for Eliciting Protective Immune Responses

by Mireia Pelegrin, Soledad Marsile-Medun, Daouda Abba-Moussa, Manon Souchard and Mar Naranjo-Gomez

Antibodies 2022, 11(3), 50; https://doi.org/10.3390/antib11030050 - 26 Jul 2022

Cited by 1 | Viewed by 3090

Abstract

The multiple mechanisms of action of antiviral monoclonal antibodies (mAbs) have made these molecules a potential therapeutic alternative for treating severe viral infections. In addition to their direct effect on viral propagation, several studies have shown that mAbs are able to enhance the [...] Read more.

The multiple mechanisms of action of antiviral monoclonal antibodies (mAbs) have made these molecules a potential therapeutic alternative for treating severe viral infections. In addition to their direct effect on viral propagation, several studies have shown that mAbs are able to enhance the host’s adaptive immune response and generate long-lasting protective immunity. Such immunomodulatory effects occur in an Fc-dependent manner and rely on Fc-FcγR interactions. It is noteworthy that several FcγR-expressing cells have been shown to play a key role in enhancing humoral and cellular immune responses (so-called “vaccinal effects”) in different experimental settings. This review recalls recent findings concerning the vaccinal effects induced by antiviral mAbs, both in several preclinical animal models and in patients treated with mAbs. It summarizes the main cellular and molecular mechanisms involved in these immunomodulatory properties of antiviral mAbs identified in different pathological contexts. It also describes potential therapeutic interventions to enhance host immune responses that could guide the design of improved mAb-based immunotherapies. Full article

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

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20 pages, 11965 KiB

Open AccessEditor’s ChoiceReview

Therapeutic Potential of Intrabodies for Cancer Immunotherapy: Current Status and Future Directions

by Thomas Böldicke

Antibodies 2022, 11(3), 49; https://doi.org/10.3390/antib11030049 - 18 Jul 2022

Cited by 11 | Viewed by 5325

Abstract

Tumor cells are characterized by overexpressed tumor-associated antigens or mutated neoantigens, which are expressed on the cell surface or intracellularly. One strategy of cancer immunotherapy is to target cell-surface-expressed tumor-associated antigens (TAAs) with therapeutic antibodies. For targeting TAAs or neoantigens, adoptive T-cell therapies [...] Read more.

Tumor cells are characterized by overexpressed tumor-associated antigens or mutated neoantigens, which are expressed on the cell surface or intracellularly. One strategy of cancer immunotherapy is to target cell-surface-expressed tumor-associated antigens (TAAs) with therapeutic antibodies. For targeting TAAs or neoantigens, adoptive T-cell therapies with activated autologous T cells from cancer patients transduced with novel recombinant TCRs or chimeric antigen receptors have been successfully applied. Many TAAs and most neoantigens are expressed in the cytoplasm or nucleus of tumor cells. As alternative to adoptive T-cell therapy, the mRNA of intracellular tumor antigens can be depleted by RNAi, the corresponding genes or proteins deleted by CRISPR-Cas or inactivated by kinase inhibitors or by intrabodies, respectively. Intrabodies are suitable to knockdown TAAs and neoantigens without off-target effects. RNA sequencing and proteome analysis of single tumor cells combined with computational methods is bringing forward the identification of new neoantigens for the selection of anti-cancer intrabodies, which can be easily performed using phage display antibody repertoires. For specifically delivering intrabodies into tumor cells, the usage of new capsid-modified adeno-associated viruses and lipid nanoparticles coupled with specific ligands to cell surface receptors can be used and might bring cancer intrabodies into the clinic. Full article

(This article belongs to the Special Issue Antibody Drug and Target Discovery for Cancer Therapies)

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22 pages, 2007 KiB

Open AccessReview

Understanding and Modulating Antibody Fine Specificity: Lessons from Combinatorial Biology

by Gertrudis Rojas

Antibodies 2022, 11(3), 48; https://doi.org/10.3390/antib11030048 - 14 Jul 2022

Cited by 4 | Viewed by 7367

Abstract

Combinatorial biology methods such as phage and yeast display, suitable for the generation and screening of huge numbers of protein fragments and mutated variants, have been useful when dissecting the molecular details of the interactions between antibodies and their target antigens (mainly those [...] Read more.

Combinatorial biology methods such as phage and yeast display, suitable for the generation and screening of huge numbers of protein fragments and mutated variants, have been useful when dissecting the molecular details of the interactions between antibodies and their target antigens (mainly those of protein nature). The relevance of these studies goes far beyond the mere description of binding interfaces, as the information obtained has implications for the understanding of the chemistry of antibody–antigen binding reactions and the biological effects of antibodies. Further modification of the interactions through combinatorial methods to manipulate the key properties of antibodies (affinity and fine specificity) can result in the emergence of novel research tools and optimized therapeutics. Full article

(This article belongs to the Special Issue Women's Special Issue Series: Recent Development for Improved Therapeutic Antibodies)

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21 pages, 1407 KiB

Open AccessEditor’s ChoiceReview

Antibody-Based Approaches to Target Pancreatic Tumours

by Marie Sorbara, Pierre Cordelier and Nicolas Bery

Antibodies 2022, 11(3), 47; https://doi.org/10.3390/antib11030047 - 12 Jul 2022

Cited by 8 | Viewed by 5311

Abstract

Pancreatic cancer is an aggressive cancer with a dismal prognosis. This is due to the difficulty to detect the disease at an early and curable stage. In addition, only limited treatment options are available, and they are confronted by mechanisms of resistance. Monoclonal [...] Read more.

Pancreatic cancer is an aggressive cancer with a dismal prognosis. This is due to the difficulty to detect the disease at an early and curable stage. In addition, only limited treatment options are available, and they are confronted by mechanisms of resistance. Monoclonal antibody (mAb) molecules are highly specific biologics that can be directly used as a blocking agent or modified to deliver a drug payload depending on the desired outcome. They are widely used to target extracellular proteins, but they can also be employed to inhibit intracellular proteins, such as oncoproteins. While mAbs are a class of therapeutics that have been successfully employed to treat many cancers, they have shown only limited efficacy in pancreatic cancer as a monotherapy so far. In this review, we will discuss the challenges, opportunities and hopes to use mAbs for pancreatic cancer treatment, diagnostics and imagery. Full article

(This article belongs to the Special Issue Antibody Drug and Target Discovery for Cancer Therapies)

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16 pages, 4376 KiB

Open AccessEditor’s ChoiceReview

3D Models as a Tool to Assess the Anti-Tumor Efficacy of Therapeutic Antibodies: Advantages and Limitations

by Virginia Guzzeloni, Lorenzo Veschini, Federica Pedica, Elisabetta Ferrero and Marina Ferrarini

Antibodies 2022, 11(3), 46; https://doi.org/10.3390/antib11030046 - 8 Jul 2022

Cited by 5 | Viewed by 4116

Abstract

Therapeutic monoclonal antibodies (mAbs) are an emerging and very active frontier in clinical oncology, with hundred molecules currently in use or being tested. These treatments have already revolutionized clinical outcomes in both solid and hematological malignancies. However, identifying patients who are most likely [...] Read more.

Therapeutic monoclonal antibodies (mAbs) are an emerging and very active frontier in clinical oncology, with hundred molecules currently in use or being tested. These treatments have already revolutionized clinical outcomes in both solid and hematological malignancies. However, identifying patients who are most likely to benefit from mAbs treatment is currently challenging and limiting the impact of such therapies. To overcome this issue, and to fulfill the expectations of mAbs therapies, it is urgently required to develop proper culture models capable of faithfully reproducing the interactions between tumor and its surrounding native microenvironment (TME). Three-dimensional (3D) models which allow the assessment of the impact of drugs on tumors within its TME in a patient-specific context are promising avenues to progressively fill the gap between conventional 2D cultures and animal models, substantially contributing to the achievement of personalized medicine. This review aims to give a brief overview of the currently available 3D models, together with their specific exploitation for therapeutic mAbs testing, underlying advantages and current limitations to a broader use in preclinical oncology. Full article

(This article belongs to the Special Issue Women's Special Issue Series: Recent Development for Improved Therapeutic Antibodies)

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16 pages, 1638 KiB

Open AccessEditor’s ChoiceReview

FcγR-Mediated Trogocytosis 2.0: Revisiting History Gives Rise to a Unifying Hypothesis

by Margaret A. Lindorfer and Ronald P. Taylor

Antibodies 2022, 11(3), 45; https://doi.org/10.3390/antib11030045 - 5 Jul 2022

Cited by 10 | Viewed by 3785

Abstract

There is increasing interest in the clinical implications and immunology of trogocytosis, a process in which the receptors on acceptor cells remove and internalize cognate ligands from donor cells. We have reported that this phenomenon occurs in cancer immunotherapy, in which cells that [...] Read more.

There is increasing interest in the clinical implications and immunology of trogocytosis, a process in which the receptors on acceptor cells remove and internalize cognate ligands from donor cells. We have reported that this phenomenon occurs in cancer immunotherapy, in which cells that express FcγR remove and internalize CD20 and bound mAbs from malignant B cells. This process can be generalized to include other reactions including the immune adherence phenomenon and antibody-induced immunosuppression. We discuss in detail FcγR-mediated trogocytosis and the evidence supporting a proposed predominant role for liver sinusoidal endothelial cells via the action of the inhibitory receptor FcγRIIb2. We describe experiments to test the validity of this hypothesis. The elucidation of the details of FcγR-mediated trogocytosis has the potential to allow for the development of novel therapies that can potentially block or enhance this reaction, depending upon whether the process leads to unfavorable or positive biological effects. Full article

(This article belongs to the Special Issue Women's Special Issue Series: Recent Development for Improved Therapeutic Antibodies)

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11 pages, 561 KiB

Open AccessEditor’s ChoiceReview

Deciphering the Contribution of BP230 Autoantibodies in Bullous Pemphigoid

by Connor Cole, Luca Borradori and Kyle T. Amber

Antibodies 2022, 11(3), 44; https://doi.org/10.3390/antib11030044 - 28 Jun 2022

Cited by 6 | Viewed by 5331

Abstract

Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease predominantly affecting elderly patients and carries significant morbidity and mortality. Patients typically suffer from severe itch with eczematous lesions, urticarial plaques, and/or tense blisters. BP is characterized by the presence of circulating autoantibodies against [...] Read more.

Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease predominantly affecting elderly patients and carries significant morbidity and mortality. Patients typically suffer from severe itch with eczematous lesions, urticarial plaques, and/or tense blisters. BP is characterized by the presence of circulating autoantibodies against two components of the hemidesmosome, BP180 and BP230. The transmembrane BP180, also known as type XVII collagen or BPAG2, represents the primary pathogenic autoantigen in BP, whereas the intracellular BP230 autoantigen is thought to play a minor role in disease pathogenesis. Although experimental data exist suggesting that anti-BP230 antibodies are secondarily formed following initial tissue damage mediated by antibodies targeting extracellular antigenic regions of BP180, there is emerging evidence that anti-BP230 IgG autoantibodies alone directly contribute to tissue damage. It has been further claimed that a subset of patients has a milder variant of BP driven solely by anti-BP230 autoantibodies. Furthermore, the presence of anti-BP230 autoantibodies might correlate with distinct clinical features. This review summarizes the current understanding of the role of BP230 and anti-BP230 antibodies in BP pathogenesis. Full article

(This article belongs to the Special Issue Advances in the Use of Therapeutic Antibodies and Identification of Novel Autoantibodies in Dermatologic Disease)

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11 pages, 5472 KiB

Open AccessPerspective

The Binding Landscape of Serum Antibodies: How Physical and Mathematical Concepts Can Advance Systems Immunology

by József Prechl, Krisztián Papp, Ágnes Kovács and Tamás Pfeil

Antibodies 2022, 11(3), 43; https://doi.org/10.3390/antib11030043 - 23 Jun 2022

Cited by 1 | Viewed by 2846

Abstract

Antibodies constitute a major component of serum on protein mass basis. We also know that the structural diversity of these antibodies exceeds that of all other proteins in the body and they react with an immense number of molecular targets. What we still [...] Read more.

Antibodies constitute a major component of serum on protein mass basis. We also know that the structural diversity of these antibodies exceeds that of all other proteins in the body and they react with an immense number of molecular targets. What we still cannot quantitatively describe is how antibody abundance is related to affinity, specificity, and cross reactivity. This ignorance has important practical consequences: we also do not have proper biochemical units for characterizing polyclonal serum antibody binding. The solution requires both a theoretical foundation, a physical model of the system, and technology for the experimental confirmation of theory. Here we argue that the quantitative characterization of interactions between serum antibodies and their targets requires systems-level physical chemistry approach and generates results that should help create maps of antibody binding landscape. Full article

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Antibodies, Volume 11, Issue 3 (September 2022) – 17 articles

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