Exploring the next generation of antibody–drug conjugates

Nature Reviews Clinical Oncology, Год журнала: 2024, Номер 21(3), С. 203 - 223

Опубликована: Янв. 8, 2024

Язык: Английский

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Strategies for overcoming protein and peptide instability in biodegradable drug delivery systems

Advanced Drug Delivery Reviews, Год журнала: 2023, Номер 199, С. 114904 - 114904

Опубликована: Май 30, 2023

Язык: Английский

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Protein‐based Nanoparticles: From Drug Delivery to Imaging, Nanocatalysis and Protein Therapy

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(44)

Опубликована: Март 14, 2023

Proteins and enzymes are versatile biomaterials for a wide range of medical applications due to their high specificity receptors substrates, degradability, low toxicity, overall good biocompatibility. Protein nanoparticles formed by the arrangement several native or modified proteins into nanometer-sized assemblies. In this review, we will focus on artificial nanoparticle systems, where main structural element not just an encapsulated payload. While under natural conditions, only certain form defined aggregates nanoparticles, chemical modifications change in physical environment can further extend pool available building blocks. This allows assembly many globular even enzymes. These advances preparation methods led emergence new generations nanosystems that beyond transport vehicles diverse applications, from multifunctional drug delivery imaging, nanocatalysis protein therapy.

Язык: Английский

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Reducing Immunogenicity by Design: Approaches to Minimize Immunogenicity of Monoclonal Antibodies

BioDrugs, Год журнала: 2024, Номер 38(2), С. 205 - 226

Опубликована: Янв. 23, 2024

Monoclonal antibodies (mAbs) have transformed therapeutic strategies for various diseases. Their high specificity to target antigens makes them ideal agents certain However, a challenge their application in clinical practice is potential risk induce unwanted immune response, termed immunogenicity. This drives the continued efforts deimmunize these protein therapeutics while maintaining pharmacokinetic properties and efficacy. Because mAbs hold central position against an array of diseases, importance conducting comprehensive immunogenicity assessment during drug development process cannot be overstated. Such necessitates employment silico, vitro, vivo evaluate mAbs. Understanding intricacies mechanisms that drive mAb crucial improving efficacy safety developing most effective determine mitigate immunogenic risk. review highlights recent advances prediction strategies, with focus on engineering used throughout reduce

Язык: Английский

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US FDA-approved therapeutic antibodies with high-concentration formulation: summaries and perspectives

Antibody Therapeutics, Год журнала: 2021, Номер 4(4), С. 262 - 272

Опубликована: Окт. 1, 2021

Abstract Thirty four (34) of the total US FDA approved 103 therapeutic antibody drugs, accounts for one third mAbs, are formulated with high protein concentration (100 mg/mL or above) which focus this article. The highest these mAbs is 200 mg/mL. dominant administration route subcutaneous (76%). Our analysis indicates that it may be rational to implement a platform formulation containing polysorbate, histidine and sucrose accelerate development drugs. Since 2015, approval numbers significantly increased account 76% numbers, i.e., 26 out 34 highly concentrated antibodies. Thus, we believe formulations drugs will future trend development, regardless challenges formulations.

Язык: Английский

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Instability Challenges and Stabilization Strategies of Pharmaceutical Proteins

Pharmaceutics, Год журнала: 2022, Номер 14(11), С. 2533 - 2533

Опубликована: Ноя. 20, 2022

Maintaining the structure of protein and peptide drugs has become one most important goals scientists in recent decades. Cold thermal denaturation conditions, lyophilization freeze drying, different pH concentrations, ionic strength, environmental agitation, interaction between surface liquid air as well solid, even architectural storage containers are among factors that affect stability these therapeutic biomacromolecules. The use genetic engineering, side-directed mutagenesis, fusion strategies, solvent addition various preservatives, surfactants, additives some solutions to overcome problems. This article will discuss types stress lead instabilities proteins used pharmaceutics including regulatory proteins, antibodies, antibody-drug conjugates, then all methods for fighting stresses be reviewed. New existing analytical detect instabilities, mainly changes their primary higher order structures, briefly summarized.

Язык: Английский

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Stabilization challenges and aggregation in protein-based therapeutics in the pharmaceutical industry

RSC Advances, Год журнала: 2023, Номер 13(51), С. 35947 - 35963

Опубликована: Янв. 1, 2023

Protein-based therapeutics have revolutionized the pharmaceutical industry and become vital components in development of future therapeutics. They offer several advantages over traditional small molecule drugs, including high affinity, potency specificity, while demonstrating low toxicity minimal adverse effects. However, manufacturing processes protein-based presents challenges related to protein folding, purification, stability immunogenicity that should be addressed. These proteins, like other biological molecules, are prone chemical physical instabilities. The drugs throughout entire manufacturing, storage delivery process is essential. occurrence structural instability resulting from misfolding, unfolding, modifications, as well aggregation, poses a significant risk efficacy these overshadowing their promising attributes. Gaining insight into alterations caused by aggregation impact on for advancement refinement Hence, this review, we discussed some features during production, formulation stabilization strategies engineering computational methods prevent aggregation.

Язык: Английский

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A Review of Recent Developments in Biopolymer Nano-Based Drug Delivery Systems with Antioxidative Properties: Insights into the Last Five Years

Pharmaceutics, Год журнала: 2024, Номер 16(5), С. 670 - 670

Опубликована: Май 16, 2024

In recent years, biopolymer-based nano-drug delivery systems with antioxidative properties have gained significant attention in the field of pharmaceutical research. These offer promising strategies for targeted and controlled drug while also providing antioxidant effects that can mitigate oxidative stress-related diseases. Generally, healthcare landscape is constantly evolving, necessitating continual development innovative therapeutic approaches (DDSs). DDSs play a pivotal role enhancing treatment efficacy, minimizing adverse effects, optimizing patient compliance. Among these, nanotechnology-driven garnered due to their unique properties, such as improved solubility, release, delivery. Nanomaterials, including nanoparticles, nanocapsules, nanotubes, etc., versatile platforms tissue engineering applications. Additionally, hold immense promise, leveraging natural or synthetic biopolymers encapsulate drugs enable release. numerous advantages, biocompatibility, biodegradability, low immunogenicity. The utilization polysaccharides, polynucleotides, proteins, polyesters biopolymer matrices further enhances versatility applicability DDSs. Moreover, substances emerged key players combating diseases, offering protection against cellular damage chronic illnesses. nanoformulations represents burgeoning research area, substantial increase publications years. This review provides comprehensive overview developments within this area over past five It discusses various materials, fabrication techniques, stabilizers, factors influencing degradation, it highlights emerging trends, challenges, prospects rapidly evolving field.

Язык: Английский

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Glycosylation shapes the efficacy and safety of diverse protein, gene and cell therapies

Biotechnology Advances, Год журнала: 2023, Номер 67, С. 108206 - 108206

Опубликована: Июнь 22, 2023

Over recent decades, therapeutic proteins have had widespread success in treating a myriad of diseases. Glycosylation, near universal feature this class drugs, is critical quality attribute that significantly influences the physical properties, safety profile and biological activity proteins. Optimizing protein glycosylation, therefore, offers an important avenue to developing more efficacious therapies. In review, we discuss specific examples how variations glycan structure glycoengineering impacts stability, safety, clinical efficacy protein-based drugs are already market as well those still preclinical development. We also highlight impact glycosylation on next generation biologics such T cell-based cancer therapy gene therapy.

Язык: Английский

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Automated optimisation of solubility and conformational stability of antibodies and proteins

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Апрель 6, 2023

Biologics, such as antibodies and enzymes, are crucial in research, biotechnology, diagnostics, therapeutics. Often, biologics with suitable functionality discovered, but their development is impeded by developability issues. Stability solubility key biophysical traits underpinning potential, they determine aggregation, correlate production yield poly-specificity, essential to access parenteral oral delivery. While advances for the optimisation of individual have been made, co-optimization multiple remains highly problematic time-consuming, mutations that improve one property often negatively impact others. In this work, we introduce a fully automated computational strategy simultaneous conformational stability solubility, which experimentally validate on six antibodies, including two approved Our results 42 designs demonstrate procedure effective at improving while not affecting antigen-binding. We make method available webserver www-cohsoftware.ch.cam.ac.uk.

Язык: Английский

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