Engineering Stability, Viscosity, and Immunogenicity of Antibodies by Computational Design

Kuroda, Daisuke; Tsumoto, Kouhei

doi:10.1016/j.xphs.2020.01.011

Cited by 44 publications

(44 citation statements)

References 268 publications

(326 reference statements)

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“…Despite the success of these and other approaches [ 47 , 49 , 50 , 51 , 52 ], stabilizing mutations in the CDRs or frameworks would be highly valuable. Fortunately, computational approaches for the design of antibodies with high affinity and thermostability have made significant recent advances [ 53 , 54 , 55 , 56 , 57 , 58 ]. One notable method also approaches the problem by computationally recombining antibody variable domains to generate variants with improved biophysical properties [ 53 ].…”

Section: Physical and Chemical Stabilitymentioning

confidence: 99%

Toward Drug-Like Multispecific Antibodies by Design

Sawant

Streu

et al. 2020

IJMS

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The success of antibody therapeutics is strongly influenced by their multifunctional nature that couples antigen recognition mediated by their variable regions with effector functions and half-life extension mediated by a subset of their constant regions. Nevertheless, the monospecific IgG format is not optimal for many therapeutic applications, and this has led to the design of a vast number of unique multispecific antibody formats that enable targeting of multiple antigens or multiple epitopes on the same antigen. Despite the diversity of these formats, a common challenge in generating multispecific antibodies is that they display suboptimal physical and chemical properties relative to conventional IgGs and are more difficult to develop into therapeutics. Here we review advances in the design and engineering of multispecific antibodies with drug-like properties, including favorable stability, solubility, viscosity, specificity and pharmacokinetic properties. We also highlight emerging experimental and computational methods for improving the next generation of multispecific antibodies, as well as their constituent antibody fragments, with natural IgG-like properties. Finally, we identify several outstanding challenges that need to be addressed to increase the success of multispecific antibodies in the clinic.

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Section: Physical and Chemical Stabilitymentioning

confidence: 99%

Toward Drug-Like Multispecific Antibodies by Design

Sawant

Streu

et al. 2020

IJMS

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“…Another important property in antibody drug discovery is antibody viscosity, due of its applied consequences with respect to formulation and administration. The behavior of the concentration-dependent viscosity of antibodies depends on pairwise interactions or selfassociation, which further leads to higher-order intermolecular interactions [15] (Figure 2).…”

Section: Viscositymentioning

confidence: 99%

“…Nevertheless, the trade-off between binding affinity and other properties is a concern of engineering antibodies. To conquer such an issue, a standard approach to enhance the properties of antibody is random mutagenesis based on in vitro libraries [15]. Now a day, it's relatively an ease task to engineer binding affinities with other properties through such an in vitro, library-based method by elevating temperature and controlling solution conditions during the selection process.…”

Section: Introductionmentioning

confidence: 99%

“…However, due to the advances in computational power and deep sequencing, and artificial intelligence, in silico strategies is becoming an alternate approach in engineering antibody [16]. Yet, such predictions are not completely pleasing for good two explanations, there is no straightforward protocol to design by, and the precision of in silico approach is not as good as that of in vitro libraries approach because the biophysical properties of biomolecules are not well understood [15,17]. In this review, I discuss the frontier in in silico engineering of antibodies properties.…”

Section: Introductionmentioning

confidence: 99%

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Antibodies Engineering by Computational Approach

Mustafa¹

2020

Preprint

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In the pre era of synthetic antibodies, pharmaceutical companies depend on finding novel drugs from medicinal plants and other traditional resources; while in present, technological advances in biology, computer and robotics give the researchers the ability to rewrite and edit DNA in order to synthesize very large sets of drug candidates; these novel and improved candidates serves the basis for creating another library of drug candidates and so on until we find the right biomolecule for the disease of interest. all these technologies combined together to synthesize therapeutic antibodies for many types of cancer, autoimmune diseases, and infectious diseases, that can address diseases much more readily to very rapidly get therapeutics into patients so that we can potentially have an impact on disease. The antibodies mechanism is recognize and bind to disease cells and pinpoint the immune system to attack those cells effectively. Now a days, they dependent on computational approach to guide and accelerate the process of antibodies engineering by combination of selection system and use of high-throughput data acquisition and analysis to build and construct populations of next generation antibodies that are thermo-stable, non-immunogenic as possible, and to be administered to many humans as possible. In this review, I will discuss the latest in silico methods for antibodies engineering.

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“…Computer aided antibody humanization has became an efficient and rapid routine process[Tsuchiya and Mizuguchi, 2016; Nowak et al, 2016; Nguyen et al, 2017; Regep et al, 2017; Kuroda et al, 2020; Sawant et al, 2020]. Many humanized antibodies have been developed by this method[Fransson et al, 2010; Apgar et al, 2016; Margreitter et al, 2016].…”

Section: Introductionmentioning

confidence: 99%

Optimized antibody humanization by intra and inter VH-VL binding energy sorting

Lou

2021

Preprint

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Humanization of non-human derived antibody is necessary to reduce the immunogenicity of antibody drug. In recent years, computer aided antibody humanization became an efficient and rapid routine process. We report here a new computational humanization pipeline which includes CDR grafting onto the crystal structures of homologous antibody and CDR grafted humanized antibody structures. Then, the intra and inter VH-VL binding energies are calculated and sorted for optimized humanized antibody. The resulted humanized antibodies are ranked and compared to experimental dataset, which confirms the validity of humanized antibody design by intra and inter VH-VL binding energy.

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Engineering Stability, Viscosity, and Immunogenicity of Antibodies by Computational Design

Cited by 44 publications

References 268 publications

Toward Drug-Like Multispecific Antibodies by Design

Toward Drug-Like Multispecific Antibodies by Design

Antibodies Engineering by Computational Approach

Optimized antibody humanization by intra and inter VH-VL binding energy sorting

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