Michael Hust

Bio: Michael Hust is an academic researcher from Braunschweig University of Technology. The author has contributed to research in topics: Phage display & Antibody. The author has an hindex of 39, co-authored 152 publications receiving 5130 citations. Previous affiliations of Michael Hust include Huazhong University of Science and Technology & University of Stuttgart.

Designing Human Antibodies by Phage Display

Abstract: With six approved products and more than 60 candidates in clinical testing, human monoclonal antibody discovery by phage display is well established as a robust and reliable source for the generation of therapeutic antibodies. While a vast diversity of library generation philosophies and selection strategies have been conceived, the power of molecular design offered by controlling the in vitro selection step is still to be recognized by a broader audience outside of the antibody engineering community. Here, we summarize some opportunities and achievements, e.g., the generation of antibodies which could not be generated otherwise, and the design of antibody properties by different panning strategies, including the adjustment of kinetic parameters.

Expression of recombinant Antibodies

Abstract: Recombinant antibodies are highly specific detection probes in research, diagnostics and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines and transgenic plants are promising to obtain antibodies with “human-like” post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.

Phage display-derived human antibodies in clinical development and therapy

Abstract: Over the last 3 decades, monoclonal antibodies have become the most important class of therapeutic biologicals on the market. Development of therapeutic antibodies was accelerated by recombinant DNA technologies, which allowed the humanization of murine monoclonal antibodies to make them more similar to those of the human body and suitable for a broad range of chronic diseases like cancer and autoimmune diseases. In the early 1990s in vitro antibody selection technologies were developed that enabled the discovery of “fully” human antibodies with potentially superior clinical efficacy and lowest immunogenicity.Antibody phage display is the first and most widely used of the in vitro selection technologies. It has proven to be a robust, versatile platform technology for the discovery of human antibodies and a powerful engineering tool to improve antibody properties. As of the beginning of 2016, 6 human antibodies discovered or further developed by phage display were approved for therapy. In 2002, ada...

A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV.

Abstract: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein at 3.1-angstrom resolution. CR3022 targets a highly conserved epitope, distal from the receptor binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBDs on the trimeric S protein are in the "up" conformation and slightly rotated. These results provide molecular insights into antibody recognition of SARS-CoV-2.

Selecting and screening recombinant antibody libraries

Abstract: During the past decade several display methods and other library screening techniques have been developed for isolating monoclonal antibodies (mAbs) from large collections of recombinant antibody fragments. These technologies are now widely exploited to build human antibodies with high affinity and specificity. Clever antibody library designs and selection concepts are now able to identify mAb leads with virtually any specificity. Innovative strategies enable directed evolution of binding sites with ultra-high affinity, high stability and increased potency, sometimes to a level that cannot be achieved by immunization. Automation of the technology is making it possible to identify hundreds of different antibody leads to a single therapeutic target. With the first antibody of this new generation, adalimumab (Humira, a human IgG1 specific for human tumor necrosis factor (TNF)), already approved for therapy and with many more in clinical trials, these recombinant antibody technologies will provide a solid basis for the discovery of antibody-based biopharmaceuticals, diagnostics and research reagents for decades to come.

Development of therapeutic antibodies for the treatment of diseases

Abstract: It has been more than three decades since the first monoclonal antibody was approved by the United States Food and Drug Administration (US FDA) in 1986, and during this time, antibody engineering has dramatically evolved. Current antibody drugs have increasingly fewer adverse effects due to their high specificity. As a result, therapeutic antibodies have become the predominant class of new drugs developed in recent years. Over the past five years, antibodies have become the best-selling drugs in the pharmaceutical market, and in 2018, eight of the top ten bestselling drugs worldwide were biologics. The global therapeutic monoclonal antibody market was valued at approximately US$115.2 billion in 2018 and is expected to generate revenue of $150 billion by the end of 2019 and $300 billion by 2025. Thus, the market for therapeutic antibody drugs has experienced explosive growth as new drugs have been approved for treating various human diseases, including many cancers, autoimmune, metabolic and infectious diseases. As of December 2019, 79 therapeutic mAbs have been approved by the US FDA, but there is still significant growth potential. This review summarizes the latest market trends and outlines the preeminent antibody engineering technologies used in the development of therapeutic antibody drugs, such as humanization of monoclonal antibodies, phage display, the human antibody mouse, single B cell antibody technology, and affinity maturation. Finally, future applications and perspectives are also discussed.

Davidson's Principles and Practice of Medicine

Abstract: I first read Davidson 30 years ago: at that time it was already in its 5th edition. A brief comparison shows that it then contained about 440,000 words in 1,100 pages: the current edition has compressed 625,000 words into 800 pages. I think I bought it as a student because it was cheap: but also because it seemed to be comprehensive and straightforward, and I have used it as a basis for my medical knowledge ever since. So I miss some of the old pictures of the acute skin rashes such as scarlet fever: in fact infectious disease has been transferred to the back and genetic factors take the first chapters. But careful linguistic comparison will still uncover the old phrases which some of us know by heart-there are minor changes such as 'alarming reactions to intravenous iron are uncommon, but have occasionally been noted', which becomes 'alarming systemic anaphyllactic reactions can occur'. Sir Stanley Davidson made 'no attempt to describe every rare disease or syndrome, but devoted most of the space available to those disorders most commonly encountered in practice'. I have grown up with successive editions, and have gradually come to appreciate the problems of the authors in the compression of knowledge. Having got to know many of them personally as real people rather than as names I can still recommend the book. It is the essential starting point for the study of internal medicine and for many doctors will remain their base reference work. The present editors have kept up-to-date and been prepared to prune the dead wood. There are many competitors in the market, and the publishers must take care with layout and illustration, although Davidson is still the best value for money. I will continue to recommend it to my clinical students: they will need to read it and know it to pass final MB. Postgraduates will need to remember the facts, but also to be able to place them in a broader perspective. The older consultant will still happily read it, and to get to know the authors themselves is really to complete your medical education. Dr John Macleod and his team have successfully kept alive the primary objective 'to provide a rational and easily comprehensible basis for the practice of medicine'. The book is economical in price and compact in size, but still contains the essential truths for the practice of good medicine.

The Current State of Peptide Drug Discovery: Back to the Future?

Abstract: Over the past decade, peptide drug discovery has experienced a revival of interest and scientific momentum, as the pharmaceutical industry has come to appreciate the role that peptide therapeutics can play in addressing unmet medical needs and how this class of compounds can be an excellent complement or even preferable alternative to small molecule and biological therapeutics. In this Perspective, we give a concise description of the recent progress in peptide drug discovery in a holistic manner, highlighting enabling technological advances affecting nearly every aspect of this field: from lead discovery, to synthesis and optimization, to peptide drug delivery. An emphasis is placed on describing research efforts to overcome the inherent weaknesses of peptide drugs, in particular their poor pharmacokinetic properties, and how these efforts have been critical to the discovery, design, and subsequent development of novel therapeutics.