Therapeutic Antibody Development: What Are We Learning along the Way? 2.0

Dear Colleagues,

There is now ample evidence that monoclonal antibodies are very powerful drugs, fulfilling many unmet medical needs. There were only 20 approved recombinant antibodies in 2008, but this number has now reached more than 100, and hundreds are undergoing clinical trials, covering all therapeutic areas. As the properties needed for an antibody to be a good drug differ from those of natural and even pathogenic antibodies, many new scientific questions have arisen from pharmacological and pharmaceutical questions.

It clearly appears that, as often occurs in science, the more answers we bring, the more questions we get, making the discovery and development of therapeutic antibodies a perpetual questioning engine. The IgG1 subclass has been largely privileged, but many other natural or engineered heavy-chain isotypes are now available to adapt molecules to the pharmacological or pharmaceutical needs of long half-lives, reduced immunogenicity, reduced or sometimes increased immune activation, etc. A great effort of creativity has led to bi- or multispecific antibodies with totally new properties, bringing antigens, receptors and cells together. Observing and investigating the side effects of antibodies on very large cohorts has revealed off-target side effects, leading to the conclusion that antibodies are not as specific as we thought, reviving the questions of polyreactivity and polyspecificity. As we gain deeper knowledge on the mode of action, there is also increasing interest in playing with physico-chemical properties such as the pH dependence of either Fc-FcRn or Ag-Ab binding or even both. Another aspect is that, at present, the discovery and development process takes 5 to 10 years, with an attrition rate of 0.95. Many methods are being developed to secure and accelerate this process.

In this Special Issue, we will review some of these questions and how they may lead to important scientific advances. Papers related to any molecular aspects of antibodies, including bioinformatics studies, will be considered for this Special Issue.

Dr. Anne Poupon
Prof. Dr. Hervé Watier
Guest Editors

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