Therapeutic Antibodies

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (31 October 2017) | Viewed by 28673

Special Issue Editor

Structural Biology, UCB, 216 Bath Road, Slough SL1 3WE, UK
Interests: therapeutic antibodies; antibody technology; antibody fragments; molecular dynamics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the last thirty years, therapeutic antibodies have gone from “not existing” to being the world’s top prescription drugs, largely through their ability to bring protein-protein interactions into play in medicine. This Special Issue of Antibodies charts the rise of therapeutic antibodies and acknowledges the technological hurdles that have been overcome to make them front line therapies. In addition, we will address the limitations of such products, such as potential immunogenicity, supply chain complexity and cost of treatment. Finally the Special Issue will cover alternative therapeutic modalities, which represent potential disruptive technologies for antibodies in the future.

Dr. Alastair Lawson
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibodies is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • therapeutic antibodies

  • immunogenicity

  • supply chain complexity

  • cost of goods

  • small molecules targeting protein-protein interactions

Published Papers (3 papers)

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Review

22 pages, 1677 KiB  
Review
Therapeutic Antibody-Like Immunoconjugates against Tissue Factor with the Potential to Treat Angiogenesis-Dependent as Well as Macrophage-Associated Human Diseases
Antibodies 2018, 7(1), 8; https://doi.org/10.3390/antib7010008 - 23 Jan 2018
Cited by 9 | Viewed by 8019
Abstract
Accumulating evidence suggests that tissue factor (TF) is selectively expressed in pathological angiogenesis-dependent as well as macrophage-associated human diseases. Pathological angiogenesis, the formation of neovasculature, is involved in many clinically significant human diseases, notably cancer, age-related macular degeneration (AMD), endometriosis and rheumatoid arthritis [...] Read more.
Accumulating evidence suggests that tissue factor (TF) is selectively expressed in pathological angiogenesis-dependent as well as macrophage-associated human diseases. Pathological angiogenesis, the formation of neovasculature, is involved in many clinically significant human diseases, notably cancer, age-related macular degeneration (AMD), endometriosis and rheumatoid arthritis (RA). Macrophage is involved in the progression of a variety of human diseases, such as atherosclerosis and viral infections (human immunodeficiency virus, HIV and Ebola). It is well documented that TF is selectively expressed on angiogenic vascular endothelial cells (VECs) in these pathological angiogenesis-dependent human diseases and on disease-associated macrophages. Under physiology condition, TF is not expressed by quiescent VECs and monocytes but is solely restricted on some cells (such as pericytes) that are located outside of blood circulation and the inner layer of blood vessel walls. Here, we summarize TF expression on angiogenic VECs, macrophages and other diseased cell types in these human diseases. In cancer, for example, the cancer cells also overexpress TF in solid cancers and leukemia. Moreover, our group recently reported that TF is also expressed by cancer-initiating stem cells (CSCs) and can serve as a novel oncotarget for eradication of CSCs without drug resistance. Furthermore, we review and discuss two generations of TF-targeting therapeutic antibody-like immunoconjugates (ICON and L-ICON1) and antibody-drug conjugates that are currently being tested in preclinical and clinical studies for the treatment of some of these human diseases. If efficacy and safety are proven in current and future clinical trials, TF-targeting immunoconjugates may provide novel therapeutic approaches with potential to broadly impact the treatment regimen of these significant angiogenesis-dependent, as well as macrophage-associated, human diseases. Full article
(This article belongs to the Special Issue Therapeutic Antibodies)
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19 pages, 3026 KiB  
Review
Enzyme-Based Labeling Strategies for Antibody–Drug Conjugates and Antibody Mimetics
Antibodies 2018, 7(1), 4; https://doi.org/10.3390/antib7010004 - 04 Jan 2018
Cited by 38 | Viewed by 12754
Abstract
Strategies for site-specific modification of proteins have increased in number, complexity, and specificity over the last years. Such modifications hold the promise to broaden the use of existing biopharmaceuticals or to tailor novel proteins for therapeutic or diagnostic applications. The recent quest for [...] Read more.
Strategies for site-specific modification of proteins have increased in number, complexity, and specificity over the last years. Such modifications hold the promise to broaden the use of existing biopharmaceuticals or to tailor novel proteins for therapeutic or diagnostic applications. The recent quest for next-generation antibody–drug conjugates (ADCs) sparked research into techniques with site selectivity. While purely chemical approaches often impede control of dosage or locus of derivatization, naturally occurring enzymes and proteins bear the ability of co- or post-translational protein modifications at particular residues, thus enabling unique coupling reactions or protein fusions. This review provides a general overview and focuses on chemo-enzymatic methods including enzymes such as formylglycine-generating enzyme, sortase, and transglutaminase. Applications for the conjugation of antibodies and antibody mimetics are reported. Full article
(This article belongs to the Special Issue Therapeutic Antibodies)
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480 KiB  
Review
Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders
Antibodies 2017, 6(4), 19; https://doi.org/10.3390/antib6040019 - 21 Nov 2017
Cited by 10 | Viewed by 7427
Abstract
The effector functions of T lymphocytes are responsible for most autoimmune disorders and act by directly damaging tissues or by indirectly promoting inflammation and antibody responses. Co-stimulatory and co-inhibitory T cell receptor molecules are the primary pharmacological targets that enable interference with immune-mediated [...] Read more.
The effector functions of T lymphocytes are responsible for most autoimmune disorders and act by directly damaging tissues or by indirectly promoting inflammation and antibody responses. Co-stimulatory and co-inhibitory T cell receptor molecules are the primary pharmacological targets that enable interference with immune-mediated diseases. Among these, selective CD28 antagonists have drawn special interest, since they tip the co-stimulation/co-inhibition balance towards efficiently inhibiting effector T cells while promoting suppression by pre-existing regulatory T-cells. After having demonstrated outstanding therapeutic efficacy in multiple models of autoimmunity, inflammation and transplantation, and safety in phase-I studies in humans, selective CD28 antagonists are currently in early clinical development for the treatment of systemic lupus erythematous and rheumatoid arthritis. Here, we review the available proof of concept studies for CD28 antagonists in autoimmunity, with a special focus on the mechanisms of action. Full article
(This article belongs to the Special Issue Therapeutic Antibodies)
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