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  • Review
  • Open Access
555 Citations
112,740 Views
80 Pages

Antibody Structure and Function: The Basis for Engineering Therapeutics

  • Mark L. Chiu,
  • Dennis R. Goulet,
  • Alexey Teplyakov and
  • Gary L. Gilliland

3 December 2019

Antibodies and antibody-derived macromolecules have established themselves as the mainstay in protein-based therapeutic molecules (biologics). Our knowledge of the structure–function relationships of antibodies provides a platform for protein e...

(This article belongs to the Special Issue Structure and Function of Antibodies)
  • Feature Paper
  • Review
  • Open Access
741 Citations
57,203 Views
20 Pages

Monoclonal Antibodies in Cancer Therapy

  • David Zahavi and
  • Louis Weiner

Monoclonal antibody-based immunotherapy is now considered to be a main component of cancer therapy, alongside surgery, radiation, and chemotherapy. Monoclonal antibodies possess a diverse set of clinically relevant mechanisms of action. In addition,...

(This article belongs to the Special Issue Antibody Engineering for Cancer Immunotherapy)
  • Review
  • Open Access
260 Citations
51,013 Views
30 Pages

Design and Production of Bispecific Antibodies

  • Qiong Wang,
  • Yiqun Chen,
  • Jaeyoung Park,
  • Xiao Liu and ,
  • Yifeng Hu,
  • Tiexin Wang,
  • Kevin McFarland and
  • Michael J. Betenbaugh
  • + 3 authors+ 0 author

2 August 2019

With the current biotherapeutic market dominated by antibody molecules, bispecific antibodies represent a key component of the next-generation of antibody therapy. Bispecific antibodies can target two different antigens at the same time, such as simu...

(This article belongs to the Special Issue Structure and Function of Antibodies)
  • Review
  • Open Access
242 Citations
45,157 Views
30 Pages

IgA: Structure, Function, and Developability

  • Patrícia de Sousa-Pereira and
  • Jenny M. Woof

5 December 2019

Immunoglobulin A (IgA) plays a key role in defending mucosal surfaces against attack by infectious microorganisms. Such sites present a major site of susceptibility due to their vast surface area and their constant exposure to ingested and inhaled ma...

(This article belongs to the Special Issue Structure and Function of Antibodies)
  • Review
  • Open Access
119 Citations
45,024 Views
16 Pages

In Vivo Applications of Single Chain Fv (Variable Domain) (scFv) Fragments

  • Philippe P. Monnier,
  • Robin J. Vigouroux and
  • Nardos G. Tassew

11 April 2013

Single chain variable domain (Fv) fragments (scFv) are powerful tools in research and clinical settings, owing to better pharmacokinetic properties compared to the parent monoclonal antibodies and the relative ease of producing them in large quantiti...

(This article belongs to the Special Issue Single-Domain Antibody)
  • Review
  • Open Access
139 Citations
44,897 Views
23 Pages

Antibody Aggregation: Insights from Sequence and Structure

  • Wei Li,
  • Ponraj Prabakaran,
  • Weizao Chen,
  • Zhongyu Zhu and ,
  • Yang Feng and
  • Dimiter S. Dimitrov
  • + 1 author+ 0 author

5 September 2016

Monoclonal antibodies (mAbs) are the fastest-growing biological therapeutics with important applications ranging from cancers, autoimmunity diseases and metabolic disorders to emerging infectious diseases. Aggregation of mAbs continues to be a major...

  • Review
  • Open Access
97 Citations
42,751 Views
19 Pages

Antibody Fragments and Their Purification by Protein L Affinity Chromatography

  • Gustav Rodrigo,
  • Mats Gruvegård and
  • James M. Van Alstine

11 September 2015

Antibodies and related proteins comprise one of the largest and fastest-growing classes of protein pharmaceuticals. A majority of such molecules are monoclonal antibodies; however, many new entities are antibody fragments. Due to their structural, ph...

(This article belongs to the Special Issue Antibody Constructs)
  • Review
  • Open Access
99 Citations
41,930 Views
23 Pages

Antibody Glycosylation and Inflammation

  • Kai-Ting C. Shade and
  • Robert M. Anthony

25 June 2013

IgG antibodies are the basis of some of the most effective therapeutics developed over the last 20 years. These antibodies are highly specific, have long serum-half lives, and can be produced relatively routinely, making them ideal drugs for immunoth...

(This article belongs to the Special Issue Modes of Antibody Action for Cancer Therapy)
  • Feature Paper
  • Review
  • Open Access
239 Citations
40,295 Views
35 Pages

Structure, Function, and Therapeutic Use of IgM Antibodies

  • Bruce A. Keyt,
  • Ramesh Baliga,
  • Angus M. Sinclair,
  • Stephen F. Carroll and
  • Marvin S. Peterson

13 October 2020

Natural immunoglobulin M (IgM) antibodies are pentameric or hexameric macro-immunoglobulins and have been highly conserved during evolution. IgMs are initially expressed during B cell ontogeny and are the first antibodies secreted following exposure...

(This article belongs to the Special Issue Structure and Function of Antibodies)
  • Feature Paper
  • Review
  • Open Access
232 Citations
39,877 Views
34 Pages

Fc-Engineering for Modulated Effector Functions—Improving Antibodies for Cancer Treatment

  • Rena Liu,
  • Robert J. Oldham,
  • Emma Teal,
  • Stephen A. Beers and
  • Mark S. Cragg

17 November 2020

The majority of monoclonal antibody (mAb) therapeutics possess the ability to engage innate immune effectors through interactions mediated by their fragment crystallizable (Fc) domain. By delivering Fc-Fc gamma receptor (FcγR) and Fc-C1q interactions...

(This article belongs to the Special Issue Antibody Engineering for Cancer Immunotherapy)
  • Review
  • Open Access
55 Citations
38,959 Views
20 Pages

IgG Antibody 3D Structures and Dynamics

  • Jacob White Jay,
  • Brinkley Bray,
  • Yaozhi Qi,
  • Eseosaserea Igbinigie and ,
  • Hao Wu,
  • Jinping Li and
  • Gang Ren
  • + 2 authors+ 0 author

19 April 2018

Antibodies are vital for human health because of their ability to function as nature’s drugs by protecting the body from infection. In recent decades, antibodies have been used as pharmaceutics for targeted therapy in patients with cancer, auto...

  • Review
  • Open Access
136 Citations
36,992 Views
49 Pages

Developments and Challenges for mAb-Based Therapeutics

  • Sumit Goswami,
  • Wei Wang,
  • Tsutomu Arakawa and
  • Satoshi Ohtake

16 August 2013

The continuous increase in the number of approved monoclonal antibody (mAb)-based therapy suggests that mAbs, and their derivatives, will continue to be the focus of the biotherapeutics industry for years to come. Although vast improvements in our ca...

(This article belongs to the Special Issue Monoclonal Antibody Preparation against Natural Product and Its Application)
  • Review
  • Open Access
103 Citations
33,563 Views
28 Pages

Antibody Conjugates: From Heterogeneous Populations to Defined Reagents

  • Patrick Dennler,
  • Eliane Fischer and
  • Roger Schibli

3 August 2015

Monoclonal antibodies (mAbs) and their derivatives are currently the fastest growing class of therapeutics. Even if naked antibodies have proven their value as successful biopharmaceuticals, they suffer from some limitations. To overcome suboptimal t...

  • Review
  • Open Access
156 Citations
33,034 Views
18 Pages

The Ligands for Human IgG and Their Effector Functions

  • Steven W. de Taeye,
  • Theo Rispens and
  • Gestur Vidarsson

25 April 2019

Activation of the humoral immune system is initiated when antibodies recognize an antigen and trigger effector functions through the interaction with Fc engaging molecules. The most abundant immunoglobulin isotype in serum is Immunoglobulin G (IgG),...

(This article belongs to the Special Issue Structure and Function of Antibodies)
  • Review
  • Open Access
128 Citations
32,728 Views
20 Pages

The development of recombinant therapeutic proteins has been a major revolution in modern medicine. Therapeutic-based monoclonal antibodies (mAbs) are growing rapidly, providing a potential class of human pharmaceuticals that can improve the manageme...

(This article belongs to the Special Issue Monoclonal Antibody-Directed Therapy)
  • Review
  • Open Access
123 Citations
32,450 Views
68 Pages

The concepts for T-cell redirecting bispecific antibodies (TRBAs) and chimeric antigen receptor (CAR)-T cells are both at least 30 years old but both platforms are just now coming into age. Two TRBAs and two CAR-T cell products have been approved by...

(This article belongs to the Special Issue Structure and Function of Antibodies)
  • Review
  • Open Access
139 Citations
31,791 Views
21 Pages

Phage Display Libraries for Antibody Therapeutic Discovery and Development

  • Juan C. Almagro,
  • Martha Pedraza-Escalona,
  • Hugo Iván Arrieta and
  • Sonia Mayra Pérez-Tapia

23 August 2019

Phage display technology has played a key role in the remarkable progress of discovering and optimizing antibodies for diverse applications, particularly antibody-based drugs. This technology was initially developed by George Smith in the mid-1980s a...

  • Review
  • Open Access
112 Citations
30,039 Views
41 Pages

IgE Antibodies: From Structure to Function and Clinical Translation

  • Brian J. Sutton,
  • Anna M. Davies,
  • Heather J. Bax and
  • Sophia N. Karagiannis

22 February 2019

Immunoglobulin E (IgE) antibodies are well known for their role in mediating allergic reactions, and their powerful effector functions activated through binding to Fc receptors FcεRI and FcεRII/CD23. Structural studies of IgE-Fc alone...

(This article belongs to the Special Issue Structure and Function of Antibodies)
  • Review
  • Open Access
11 Citations
29,724 Views
14 Pages

B Cell Tolerance in Health and Disease

  • Murali Gururajan,
  • Vishal J. Sindhava and
  • Subbarao Bondada

19 February 2014

B lymphocyte receptors are generated randomly during the bone marrow developmental phase of B cells. Hence, the B cell repertoire consists of both self and foreign antigen specificities necessitating specific tolerance mechanisms to eliminate self-re...

(This article belongs to the Special Issue B Cells and Immunological Tolerance)
  • Review
  • Open Access
49 Citations
28,276 Views
40 Pages

Targeting of Tumor Necrosis Factor Alpha Receptors as a Therapeutic Strategy for Neurodegenerative Disorders

  • Yun Dong,
  • Doortje W. Dekens,
  • Peter Paul De Deyn,
  • Petrus J. W. Naudé and
  • Ulrich L. M. Eisel

19 November 2015

Numerous studies have revealed the pleiotropic functions of tumor necrosis factor alpha (TNF-α), and have linked it with several neurodegenerative disorders. This review describes the signaling pathways induced by TNF-α via its two receptors (TNFR1 a...

  • Review
  • Open Access
217 Citations
28,184 Views
31 Pages

Since the licensing of the first monoclonal antibody therapy in 1986, monoclonal antibodies have become the largest class of biopharmaceuticals with over 80 antibodies currently approved for a variety of disease indications. The development of smalle...

(This article belongs to the Special Issue Structure and Function of Antibodies)
  • Review
  • Open Access
61 Citations
27,436 Views
22 Pages

26 January 2015

Engineered antibodies are key players in therapy, diagnostics and research. In addition to full size immunoglobulin gamma (IgG) molecules, smaller formats of recombinant antibodies, such as single-chain variable fragments (scFv) and antigen binding f...

(This article belongs to the Special Issue Antibody Constructs)
  • Review
  • Open Access
181 Citations
27,123 Views
32 Pages

4 January 2016

Systemic Lupus Erythematosus (SLE) is characterized by a wide spectrum of auto-antibodies which recognize several cellular components. The production of these self-reactive antibodies fluctuates during the course of the disease and the involvement of...

(This article belongs to the Special Issue Auto-Antibody and Autoimmune Disease)
  • Review
  • Open Access
9 Citations
27,093 Views
36 Pages

22 January 2014

The variety of chemically diverse pharmacologically-active compounds administered to patients is large and seemingly forever growing, and, with every new drug released and administered, there is always the potential of an allergic reaction. The most...

  • Article
  • Open Access
37 Citations
26,598 Views
34 Pages

Functional, Biophysical, and Structural Characterization of Human IgG1 and IgG4 Fc Variants with Ablated Immune Functionality

  • Susan H. Tam,
  • Stephen G. McCarthy,
  • Anthony A. Armstrong,
  • Sandeep Somani and ,
  • Sheng-Jiun Wu,
  • Xuesong Liu,
  • Alexis Gervais,
  • Robin Ernst,
  • Dorina Saro and
  • Bernard J. Scallon
  • + 9 authors+ 4 authors

1 September 2017

Engineering of fragment crystallizable (Fc) domains of therapeutic immunoglobulin (IgG) antibodies to eliminate their immune effector functions while retaining other Fc characteristics has numerous applications, including blocking antigens on Fc gamm...

(This article belongs to the Special Issue Monoclonal Antibodies)
  • Review
  • Open Access
69 Citations
26,488 Views
41 Pages

25 February 2022

Identification of new disease-associated biomarkers; specific targeting of such markers by monoclonal antibodies (mAbs); and application of advances in recombinant technology, including the production of humanized and fully human antibodies, has enab...

  • Review
  • Open Access
78 Citations
26,273 Views
23 Pages

Targeting sTNF/TNFR1 Signaling as a New Therapeutic Strategy

  • Roman Fischer,
  • Roland E. Kontermann and
  • Olaf Maier

6 March 2015

Deregulation of the tumor necrosis factor (TNF) plays an important role in the initiation and perpetuation of chronic inflammation and has been implicated in the development of various autoimmune diseases. Accordingly, TNF-inhibitors are successfully...

  • Article
  • Open Access
88 Citations
25,824 Views
30 Pages

Development of PF-06671008, a Highly Potent Anti-P-cadherin/Anti-CD3 Bispecific DART Molecule with Extended Half-Life for the Treatment of Cancer

  • Adam R. Root,
  • Wei Cao,
  • Bilian Li,
  • Peter LaPan and ,
  • Caryl Meade,
  • Jocelyn Sanford,
  • Macy Jin,
  • Cliona O’Sullivan,
  • Emma Cummins and
  • Laird Bloom
  • + 41 authors+ 36 authors

Bispecific antibodies offer a promising approach for the treatment of cancer but can be challenging to engineer and manufacture. Here we report the development of PF-06671008, an extended-half-life dual-affinity re-targeting (DART®) bispecific molecu...

  • Article
  • Open Access
106 Citations
25,673 Views
16 Pages

Pre-Clinical Intravenous Serum Pharmacokinetics of Albumin Binding and Non-Half-Life Extended Nanobodies®

  • Sven Hoefman,
  • Ingrid Ottevaere,
  • Judith Baumeister and
  • Maria Laura Sargentini-Maier

10 July 2015

Nanobodies are antigen-binding, single variable domain proteins derived from naturally-occurring, heavy chain only antibodies. They are highly soluble, stable, and can be linked to build multi-specific formats. Several Nanobodies are currently in cli...

  • Review
  • Open Access
123 Citations
25,595 Views
21 Pages

21 January 2019

In the last decade, cancer immunotherapies have produced impressive therapeutic results. However, the potency of immunotherapy is tightly linked to immune cell infiltration within the tumor and varies from patient to patient. Thus, it is becoming inc...

(This article belongs to the Special Issue Nanobody)
  • Review
  • Open Access
43 Citations
25,316 Views
16 Pages

12 March 2024

Catastrophic antiphospholipid syndrome (CAPS) is a rare and life-threatening condition characterized by the persistence of antiphospholipid antibodies and occurrence of multiple vascular occlusive events. CAPS currently remains a diagnostic challenge...

(This article belongs to the Section Antibody-Based Therapeutics)
  • Review
  • Open Access
54 Citations
25,315 Views
10 Pages

Engineering IgG-Like Bispecific Antibodies—An Overview

  • Simon Krah,
  • Harald Kolmar,
  • Stefan Becker and
  • Stefan Zielonka

1 August 2018

Monoclonal antibody therapeutics have proven to be successful treatment options for patients in various indications. Particularly in oncology, therapeutic concepts involving antibodies often rely on the so-called effector functions, such as antibody...

  • Review
  • Open Access
22 Citations
24,993 Views
19 Pages

17 October 2013

The human intestine is populated with an extremely dense and diverse bacterial community. Commensal bacteria act as an important antigenic stimulus producing the maturation of gut-associated lymphoid tissue (GALT). The production of immunoglobulin (I...

(This article belongs to the Special Issue B Cells and Immunological Tolerance)
  • Review
  • Open Access
23 Citations
24,992 Views
14 Pages

Diagnosis and Treatment of Paraneoplastic Neurologic Syndromes

  • Daniel Chiu,
  • John Rhee and
  • L. Nicolas Gonzalez Castro

Paraneoplastic antibody syndromes result from the anti-tumor antibody response against normal antigens ectopically expressed by tumor cells. Although this antibody response plays an important role in helping clear a nascent or established tumor, the...

  • Review
  • Open Access
111 Citations
24,580 Views
27 Pages

Antibody Conjugates-Recent Advances and Future Innovations

  • Donmienne Leung,
  • Jacqueline M. Wurst,
  • Tao Liu,
  • Ruben M. Martinez and ,
  • Amita Datta-Mannan and
  • Yiqing Feng
  • + 1 author+ 0 author

8 January 2020

Monoclonal antibodies have evolved from research tools to powerful therapeutics in the past 30 years. Clinical success rates of antibodies have exceeded expectations, resulting in heavy investment in biologics discovery and development in addition to...

(This article belongs to the Special Issue Monoclonal Antibody-Directed Therapy)
  • Review
  • Open Access
44 Citations
24,514 Views
19 Pages

Strategies for Selecting Membrane Protein-Specific Antibodies using Phage Display with Cell-Based Panning

  • Mohamed A. Alfaleh,
  • Martina L. Jones,
  • Christopher B. Howard and
  • Stephen M. Mahler

5 August 2017

Membrane proteins are attractive targets for monoclonal antibody (mAb) discovery and development. Although several approved mAbs against membrane proteins have been isolated from phage antibody libraries, the process is challenging, as it requires th...

  • Review
  • Open Access
73 Citations
24,256 Views
26 Pages

Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

  • Irina A. Pashnina,
  • Irina M. Krivolapova,
  • Tamara V. Fedotkina,
  • Varvara A. Ryabkova and ,
  • Margarita V. Chereshneva,
  • Leonid P. Churilov and
  • Valeriy A. Chereshnev
  • + 2 authors+ 0 author

25 February 2021

The incidence of autoimmune diseases is increasing. Antinuclear antibody (ANA) testing is a critical tool for their diagnosis. However, ANA prevalence in healthy persons has increased over the last decades, especially among young people. ANA in healt...

  • Review
  • Open Access
99 Citations
24,007 Views
48 Pages

4 December 2019

Monoclonal antibodies (mAbs) are currently the largest and most dominant class of therapeutic proteins. Inter-individual variability has been observed for several mAbs; however, an understanding of the underlying mechanisms and factors contributing t...

  • Feature Paper
  • Review
  • Open Access
121 Citations
23,650 Views
28 Pages

Factors Affecting the Pharmacology of Antibody–Drug Conjugates

  • Andrew T. Lucas,
  • Lauren S. L. Price,
  • Allison N. Schorzman,
  • Mallory Storrie and ,
  • Joseph A. Piscitelli,
  • Juan Razo and
  • William C. Zamboni
  • + 2 authors+ 0 author

7 February 2018

Major advances in therapeutic proteins, including antibody–drug conjugates (ADCs), have created revolutionary drug delivery systems in cancer over the past decade. While these immunoconjugate agents provide several advantages compared to their small-...

(This article belongs to the Special Issue Antibody Drug Conjugates)
  • Review
  • Open Access
74 Citations
22,446 Views
31 Pages

25 October 2017

Developing therapeutics that induce apoptosis in cancer cells has become an increasingly attractive approach for the past 30 years. The discovery of tumor necrosis factor (TNF) superfamily members and more specifically TNF-related apoptosis-inducing...

  • Article
  • Open Access
60 Citations
22,211 Views
16 Pages

Shark Variable New Antigen Receptor (VNAR) Single Domain Antibody Fragments: Stability and Diagnostic Applications

  • Katherine Griffiths,
  • Olan Dolezal,
  • Kathy Parisi,
  • Julie Angerosa and ,
  • Con Dogovski,
  • Miles Barraclough,
  • Abdulmonem Sanalla,
  • Joanne L. Casey,
  • Iveth González and
  • Michael Foley
  • + 7 authors+ 2 authors

25 January 2013

The single variable new antigen receptor domain antibody fragments (VNARs) derived from shark immunoglobulin new antigen receptor antibodies (IgNARs) represent some of the smallest known immunoglobulin-based protein scaffolds. As single domains, they...

(This article belongs to the Special Issue Single-Domain Antibody)
  • Article
  • Open Access
23 Citations
21,822 Views
12 Pages

Recombinant Antibody Production Using a Dual-Promoter Single Plasmid System

  • Stefania C. Carrara,
  • David Fiebig,
  • Jan P. Bogen,
  • Julius Grzeschik and ,
  • Björn Hock and
  • Harald Kolmar
  • + 1 author+ 0 author

Monoclonal antibodies (mAbs) have demonstrated tremendous effects on the treatment of various disease indications and remain the fastest growing class of therapeutics. Production of recombinant antibodies is performed using mammalian expression syste...

(This article belongs to the Special Issue Design, Production and Characterization of Peptide Antibodies)
  • Review
  • Open Access
55 Citations
21,222 Views
26 Pages

Molecular Engineering of Therapeutic Cytokines

  • Rodrigo Vazquez-Lombardi,
  • Brendan Roome and
  • Daniel Christ

3 July 2013

Over the past three decades, a large body of work has been directed at the development of therapeutic cytokines. Despite their central role in immune modulation, only a handful of cytokine therapeutics has achieved regulatory approval. One of the maj...

  • Review
  • Open Access
4 Citations
20,865 Views
33 Pages

Regulation of Germinal Center Reactions by B and T Cells

  • Young Uk Kim,
  • Xindong Liu,
  • Shinya Tanaka,
  • Dat Quoc Tran and
  • Yeonseok Chung

23 October 2013

Break of B cell tolerance to self-antigens results in the development of autoantibodies and, thus, leads to autoimmunity. How B cell tolerance is maintained during active germinal center (GC) reactions is yet to be fully understood. Recent advances r...

(This article belongs to the Special Issue B Cells and Immunological Tolerance)
  • Article
  • Open Access
25 Citations
20,795 Views
10 Pages

2 April 2014

We designed a vector for the bacterial expression of recombinant antibodies fused to a double tag composed of 6xHis and the EPEA amino acid sequence. EPEA sequence (C tag) is tightly bound by a commercial antibody when expressed at the C-term end of...

(This article belongs to the Special Issue Antibody Constructs)
  • Review
  • Open Access
86 Citations
20,722 Views
23 Pages

Therapeutic antibody technology heavily dominates the biologics market and continues to present as a significant industrial interest in developing novel and improved antibody treatment strategies. Many noteworthy advancements in the last decades have...

(This article belongs to the Special Issue Monoclonal Antibody-Directed Therapy)
  • Review
  • Open Access
26 Citations
20,709 Views
23 Pages

Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies, the Path Forward?

  • Joanie Del Bano,
  • Patrick Chames,
  • Daniel Baty and
  • Brigitte Kerfelec

26 December 2015

As evidenced by the recent approvals of Removab (EU, Trion Pharma) in 2009 and of Blincyto (US, Amgen) in 2014, the high potential of bispecific antibodies in the field of immuno-oncology is eliciting a renewed interest from pharmaceutical companies....

  • Review
  • Open Access
84 Citations
20,665 Views
18 Pages

The development of anti-drug antibodies (ADAs) following administration of biotherapeutics to patients is a vexing problem that is attracting increasing attention from pharmaceutical and biotechnology companies. This serious clinical problem is also...

  • Review
  • Open Access
67 Citations
20,517 Views
22 Pages

The Usefulness of Thyroid Antibodies in the Diagnostic Approach to Autoimmune Thyroid Disease

  • Hernando Vargas-Uricoechea,
  • Juan Patricio Nogueira,
  • María V. Pinzón-Fernández and
  • Diego Schwarzstein

Autoimmune thyroid disease (AITD) refers to a spectrum of various diseases, with two extremes of clinical presentation, hypothyroidism (Hashimoto’s thyroiditis (HT) and hyperthyroidism (Graves–Basedow disease (GBD)). Both conditions are c...

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Antibodies - ISSN 2073-4468