Advances in Antibody Design

Tiller, Kathryn E.; Tessier, Peter M.

doi:10.1146/annurev-bioeng-071114-040733

Cited by 206 publications

(175 citation statements)

References 151 publications

(209 reference statements)

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“…With advances in mAb technology, a number of approaches enable the targeting of multiple molecular species by a single therapeutic 116. For example, ABT-122 is a so-called dual variable domain mAb against both IL-17 and TNF-α.…”

Section: Newer Technologiesmentioning

confidence: 99%

Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis?

2017

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The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide. We review novel biologic agents targeting the T-helper 17 axis, including therapies directed towards interleukin (IL)-17 (secukinumab, ixekizumab, bimekizumab), IL-17R (brodalumab), IL-12/23p40 (ustekinumab, briakinumab) and IL-23p19 (guselkumab, tildrakizumab, brazikumab, risankizumab, mirikizumab). We also present an overview of biologics active against type I and II interferons, including sifalumumab, rontalizumab, anifrolumab and fontolizumab. Emerging strategies to interfere with cellular adhesion processes involved in lymphocyte recruitment are discussed, including both integrin blockade (natalizumab, vedolizumab, etrolizumab) and sphingosine-1-phosphate receptor inhibition (fingolimod, ozanimod). We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib) and second-generation selective JAK inhibitors (decernotinib, filgotinib, upadacitinib). New biologics targeting B-cells (including ocrelizumab, veltuzumab, tabalumab and atacicept) and the development of novel strategies for regulatory T-cell modulation (including low-dose IL-2 therapy and Tregitopes) are also discussed. Finally, we explore recent biotechnological advances such as the development of bispecific antibodies (ABT-122, COVA322), and their application to the treatment of IMIDs.

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Section: Newer Technologiesmentioning

confidence: 99%

Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn’s disease and ulcerative colitis?

2017

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“…The structure of antibody divides into two different biofunctional subdomains. The antigen-binding fragment (Fab) mediates antigen recognition via complementaritydetermining regions and the crystallizable fragment (Fc) recruits Fc receptor on the immune cell or the other antibody recognition [86]. Trastuzumab, an antibody for FDA-approved antibody-drug conjugate Trastuzumab emtansine, has K D = 1-7 nM for the transmembrane tyrosine kinase receptor (HER2) [87][88][89].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Recent progress in development of siRNA delivery vehicles for cancer therapy

Kim

Miyata

et al. 2016

Advanced Drug Delivery Reviews

376

305

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Recent progress in RNA biology has broadened the scope of therapeutic targets of RNA drugs for cancer therapy. However, RNA drugs, typically small interfering RNAs (siRNAs), are rapidly degraded by RNases and filtrated in the kidney, thereby requiring a delivery vehicle for efficient transport to the target cells. To date, various delivery formulations have been developed from cationic lipids, polymers, and/or inorganic nanoparticles for systemic delivery of siRNA to solid tumors. This review describes the current status of clinical trials related to siRNA-based cancer therapy, as well as the remaining issues that need to be overcome to establish a successful therapy. It, then introduces various promising design strategies of delivery vehicles for stable and targeted siRNA delivery, including the prospects for future design.

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“…Novel engineering of antibodies has potential to improve efficacy and reducing immunogenicity (mechanisms and constructs are reviewed by Scott et al [59]. and Tiller and Tessier [60]). …”

Section: General Principles and Challenges Faced By Targeting Lscmentioning

confidence: 99%