Evolution and Emergence of Therapeutic Monoclonal Antibodies

Foltz, Ian N.; Karow, Margaret; Wasserman, Scott M.

doi:10.1161/circulationaha.113.002033

Cited by 90 publications

(84 citation statements)

References 65 publications

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“…In addition, elevations in CK (0.5% evolocumab; 1.0% placebo) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT; 0.5% evolocumab, 0% placebo) were rare. As evolocumab is a monoclonal antibody, patients were actively monitored for hypersensitivity-and immunogenicity-related side effects, such as injection-site reactions and antidrug antibodies: 25 4 patients in the evolocumab group reported potential injection-site reactions, and none of the evolocumab-treated patients was found to have antidrug antibodies (binding or neutralizing). One patient in the placebo group was reported to have a positive evolocumab-binding antibody titer at the week 12 visit.…”

Section: Discussionmentioning

confidence: 99%

Effects of Evolocumab (AMG 145), a Monoclonal Antibody to PCSK9, in Hypercholesterolemic, Statin-Treated Japanese Patients at High Cardiovascular Risk

Hirayama

Honarpour

Yoshida

et al. 2014

Circ J

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Section: Discussionmentioning

confidence: 99%

Effects of Evolocumab (AMG 145), a Monoclonal Antibody to PCSK9, in Hypercholesterolemic, Statin-Treated Japanese Patients at High Cardiovascular Risk

Hirayama

Honarpour

Yoshida

et al. 2014

Circ J

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“…Antibody therapy dates back to the nineteenth century, when immunized animal sera were used to treat diseases such as diphtheria and tetanus [89]. The first mAb, muromonab-CD3, was approved in 1986 and since then our knowledge of immunogenicity has significantly expanded with a broad range of clinical applicability [90].…”

Section: Cgrp Monoclonal Antibodies (Mabs)mentioning

confidence: 99%

Targeting CGRP: A New Era for Migraine Treatment

Goldberg

Silberstein

2015

CNS Drugs

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Migraine is a highly prevalent headache disease that typically affects patients during their most productive years. Despite significant progress in understanding the underlying pathophysiology of this disorder, its treatment so far continues to depend on drugs that, in their majority, were not specifically designed for this purpose. The neuropeptide calcitonin gene-related peptide (CGRP) has been indicated as playing a critical role in the central and peripheral pathways leading to a migraine attack. It is not surprising that drugs designed to specifically block its action are gaining remarkable attention from researchers in the field with, at least so far, a safe risk profile. In this article, we highlight the evolution from older traditional treatments to the innovative CGRP target drugs that are revolutionizing the way to approach this debilitating neurological disease. We provide a brief introduction on pathophysiology of migraine and details on the characteristic, function, and localization of CGRP to then focus on CGRP receptor antagonists (CGRP-RAs) and CGRP monoclonal antibodies (CGRP mAbs). Key PointsThe neuropeptide calcitonin gene-related peptide (CGRP) has been indicated as playing a critical role in the central and peripheral pathways leading to a migraine attack.Targeting CGRP as a specific therapeutic tool for migraine may offer similar or even better efficacy than currently available treatments without the vasoconstrictive risk factors.Further studies are necessary to determine the exact role of CGRP receptor antagonists and CGRP monoclonal antibodies in migraine with aura, allodynia, and photophobia.

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“…Nowadays, a large spectrum of therapeutic antibodies is either already used clinically, undergoing clinical trials, or is in the pipeline. Cancer and immunologic disorders continue to be the focus of investigational therapeutic mAbs (estimated at > 500 currently across various stages of development) [261].…”

Section: Engineering Of Monoclonal Antibodies (Mabs)mentioning

confidence: 99%

“…As already mentioned, the first therapeutic antibody approved for clinical use was a murine-derived mAb, muronomab-CD3 [261]. Historically, chimerization and then humanization were the two subsequent molecular engineering processes described and applied to mAbs intended for therapeutic purposes [365,366].…”

Section: Stages In the Development Of Fully Human Therapeutic Antibodiesmentioning

confidence: 99%

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Applications of immunochemistry in human health: advances in vaccinology and antibody design (IUPAC Technical Report)

Klein

Templeton

Schwenk

2014

Pure and Applied Chemistry

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This report discusses the history and mechanisms of vaccination of humans as well as the engineering of therapeutic antibodies. Deeper understanding of the molecular interactions involved in both acquired and innate immunity is allowing sophistication in design of modified and even synthetic vaccines. Recombinant DNA technologies are facilitating development of DNA-based vaccines, for example, with the recognition that unmethylated CpG sequences in plasmid DNA will target Toll-like receptors on antigen-presenting cells. Formulations of DNA vaccines with increased immunogenicity include engineering into plasmids with "genetic adjuvant" capability, incorporation into polymeric or magnetic nanoparticles, and formulation with cationic polymers and other polymeric and non-polymeric coatings. Newer methods of delivery, such as particle bombardment, DNA tattooing, electroporation, and magnetic delivery, are also improving the effectiveness of DNA vaccines. RNA-based vaccines and reverse vaccinology based on gene sequencing and bioinformatic approaches are also considered. Structural vaccinology is an approach in which the detailed molecular structure of viral epitopes is used to design synthetic antigenic peptides. Virus-like particles are being designed for vaccine deliveries that are based on structures of viral capsid proteins and other synthetic lipopeptide building blocks. A new generation of adjuvants is being developed to further enhance immunogenicity, based on squalene and other oil-water emulsions, saponins, muramyl dipeptide, immunostimulatory oligonucleotides, Toll-like receptor ligands, and lymphotoxins. Finally, current trends in engineering of therapeutic antibodies including improvements of antigen-binding properties, pharmacokinetic and pharmaceutical properties, and reduction of immunogenicity are discussed. Taken together, understanding the chemistry of vaccine design, delivery and immunostimulation, and knowledge of the techniques of antibody design are allowing targeted development for the treatment of chronic disorders characterized by continuing activation of the immune system, such as autoimmune disorders, cancer, or allergies that have long been refractory to conventional approaches.

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Evolution and Emergence of Therapeutic Monoclonal Antibodies

Cited by 90 publications

References 65 publications

Effects of Evolocumab (AMG 145), a Monoclonal Antibody to PCSK9, in Hypercholesterolemic, Statin-Treated Japanese Patients at High Cardiovascular Risk

Effects of Evolocumab (AMG 145), a Monoclonal Antibody to PCSK9, in Hypercholesterolemic, Statin-Treated Japanese Patients at High Cardiovascular Risk

Targeting CGRP: A New Era for Migraine Treatment

Applications of immunochemistry in human health: advances in vaccinology and antibody design (IUPAC Technical Report)

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