Overview of Antibody Drug Delivery

Awwad, Sahar; Angkawinitwong, Ukrit

doi:10.3390/pharmaceutics10030083

Cited by 110 publications

(91 citation statements)

References 176 publications

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“…Addition of excipients to formulation buffers is broadly used to improve long-term stability. 306,323 Surfactants such as polysorbates 20 and 80 may be added to mitigate aggregation that occurs at airliquid interfaces. Similarly, amino acids such as arginine and histidine and nonreducing sugars such as sucrose and trehalose are commonly used to prevent aggregation at high protein concentrations.…”

Section: Formulationmentioning

confidence: 99%

Considerations for the Design of Antibody-Based Therapeutics

Goulet

Atkins

2020

Journal of Pharmaceutical Sciences

182

154

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Keywords: antibody(s) antibody drug(s) antibody drug conjugate(s) (ADC) physicochemical properties pharmacokinetics monoclonal antibody(s) immunotherapy IgG antibody(s) drug design developability a b s t r a c t Antibody-based proteins have become an important class of biologic therapeutics, due in large part to the stability, specificity, and adaptability of the antibody framework. Indeed, antibodies not only have the inherent ability to bind both antigens and endogenous immune receptors but also have proven extremely amenable to protein engineering. Thus, several derivatives of the monoclonal antibody format, including bispecific antibodies, antibody-drug conjugates, and antibody fragments, have demonstrated efficacy for treating human disease, particularly in the fields of immunology and oncology. Reviewed here are considerations for the design of antibody-based therapeutics, including immunological context, therapeutic mechanisms, and engineering strategies. First, characteristics of antibodies are introduced, with emphasis on structural domains, functionally important receptors, isotypic and allotypic differences, and modifications such as glycosylation. Then, aspects of therapeutic antibody design are discussed, including identification of antigen-specific variable regions, choice of expression system, use of multispecific formats, and design of antibody derivatives based on fragmentation, oligomerization, or conjugation to other functional moieties. Finally, strategies to enhance antibody function through protein engineering are reviewed while highlighting the impact of fundamental biophysical properties on protein developability.

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Section: Formulationmentioning

confidence: 99%

Considerations for the Design of Antibody-Based Therapeutics

Goulet

Atkins

2020

Journal of Pharmaceutical Sciences

182

154

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“…Proteins, especially monoclonal antibodies, and peptides are highly promising therapeutics due to their high biocompatibility, non-toxicity, biodegradability, and selectivity [54]. Nowadays, monoclonal antibodies are receiving more and more attention from scientists to serve as therapeutic agents due to their specificity and capability of blocking the activity of specific signaling molecules, cell surface markers, or enzymes [55,56]. Lundbäck and co-workers explored the therapeutic application of a partially humanized anti-high mobility group box 1 (HMGB1) monoclonal antibody in drug-induced liver injury (DILI) and ALF.…”

Section: Protein-based Approachesmentioning

confidence: 99%

Therapeutic Targeting of Hepatic Macrophages

Nijland

Bansal²

2020

Curr. Tissue Microenviron. Rep.

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Purpose of Review This review outlines the current knowledge about hepatic macrophages and provides an overview of therapeutic approaches to target hepatic macrophages for the treatment of liver diseases. Recent Findings In recent years, it has been increasingly recognized that hepatic macrophages (resident macrophages, Kupffer cells, or circulating bone marrow monocyte-derived macrophages) are implicated in liver homeostasis as well as in disease progression and resolution. More recently, different populations of hepatic macrophages with distinct phenotypes and functions have been identified that have shown to play distinct roles in the pathogenesis of various acute and chronic liver diseases. The understanding of the role of hepatic macrophages in initiation, progression, and resolution of liver diseases has given rise to the development of therapeutics that can target different phenotypes of hepatic macrophages. Innovative strategies comprises of microRNA (miRNA), small interfering RNA (siRNA), therapeutic proteins, and small-molecule inhibitors. Summary Evidence from recent in vitro and in vivo studies support the fact that hepatic macrophages can be efficiently targeted using miRNA/siRNA-based approaches, protein-based approaches, and small-molecule inhibitors for the treatment of liver diseases. However, more in-depth understanding underlying the roles of distinct macrophage phenotypes in different liver diseases is required for the translation of novel targeted therapeutics to the clinic. Keywords Hepatic macrophages. Targeted therapeutics. Liver diseases. Monocytes. Kupffer cells This article is part of the Topical Collection on Chronic Liver Disease

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“…Antibodies are an important class of biologics-based therapeutics with clear advantages of specificity and efficacy. 1,2,3 The high cost and long development times, however, present key challenges in the accessibility of monoclonal antibody therapeutics. 4,5 To quickly respond to known and new pathogens and disease, and to provide affordable, high quality treatment to patients around the globe, a molecule must be designed for activity; but it must also be made developable and safe for patients.…”

Section: Introductionmentioning

confidence: 99%

Designing Feature-Controlled Humanoid Antibody Discovery Libraries Using Generative Adversarial Networks

Amimeur

Shaver

Ketchem

et al. 2020

Preprint

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We demonstrate the use of a Generative Adversarial Network (GAN), trained from a set of over 400,000 light and heavy chain human antibody sequences, to learn the rules of human antibody formation. The resulting model surpasses common in silico techniques by capturing residue diversity throughout the variable region, and is capable of generating extremely large, diverse libraries of novel antibodies that mimic somatically hypermutated human repertoire response. This method permits us to rationally design de novo humanoid antibody libraries with explicit control over various properties of our discovery library. Through transfer learning, we are able to bias the GAN to generate molecules with key properties of interest such as improved stability and developability, lower predicted MHC Class II binding, and specific complementarity-determining region (CDR) characteristics. These approaches also provide a mechanism to better study the complex relationships between antibody sequence and molecular behavior, both in vitro and in vivo . We validate our method by successfully expressing a proof-of-concept library of nearly 100,000 GAN-generated antibodies via phage display. We present the sequences and homology-model structures of example generated antibodies expressed in stable CHO pools and evaluated across multiple biophysical properties. The creation of discovery libraries using our in silico approach allows for the control of pharmaceutical properties such that these therapeutic antibodies can provide a more rapid and cost-effective response to biological threats.

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Overview of Antibody Drug Delivery

Cited by 110 publications

References 176 publications

Considerations for the Design of Antibody-Based Therapeutics

Considerations for the Design of Antibody-Based Therapeutics

Therapeutic Targeting of Hepatic Macrophages

Designing Feature-Controlled Humanoid Antibody Discovery Libraries Using Generative Adversarial Networks

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