Comparing epitope preferences of full length and single domain antibodies

本计画将比较全长抗体与单域抗体结合部位的结构特徴。大多数抗体治疗剂是单克隆抗体（mAB），其包含整个IG分子。尽管它们作为治疗剂是成功的，但mAB的高分子量可能在生产过程中造成挑战，并可能导致组织渗透减少。由于mAB中存在片段可结晶区，它们在患者中也可能具有过度免疫原性。这导致了对单结构域抗体及其衍生物的兴趣日益增加。单结构域和全长抗体具有不同的生物物理特征，并且被认为在不同的情况下有治疗用途。迄今为止，只有一种单结构域抗体已被批准用于临床使用，但越来越多的单结构域抗体出现在临床试验中。该项目的目的是利用关于结合物-靶对的可用数据，并使用该信息来预测单个结构域或全长抗体是否将有效地靶向给定表位。这些信息将使我们能够在发现活动中研究新的蛋白质靶点时选择适当的分子形式。最终，这将为我们提供最大化潜在候选药物治疗效果的最佳机会，从而增加其进入临床的机会。该项目福尔斯属于EPSRC的“化学生物学和生物化学”研究领域，将涉及与生物技术公司Twist Bioscience的合作。

This project will compare structural features of the binding sites of full-length antibodies and single-domain antibodies. The majority of antibody therapeutics are monoclonal antibodies (mABs), comprising the entire Ig molecule. Despite their success as therapeutics, the high molecular weight of mABs can cause challenges during production and can lead to reduced tissue penetration. Due to the presence of the fragment crystallisable region in mABs, they can also be overly immunogenic in patients. This has led to an increasing interest in single domain antibodies, and their derivatives. Single domain and full length antibodies have different biophysical characteristics and are considered therapeutically useful in different contexts. So far only one single domain antibody has been approved for clinical use but an increasing number are appearing in clinical trials. The purpose of this project is to leverage available data on binder- target pairs, and to use this information to predict whether a single domain, or full length antibody will effectively target a given epitope. This information will allow us to select the appropriate molecule format when working on new protein targets within discovery campaigns. Ultimately, this will give us the best chance of maximising the therapeutic effect of a potential drug candidate, and thereby increase its chances of reaching the clinic. This project falls within the EPSRC 'chemical biology and biological chemistry' research area and will involve collaboration with biotechnology company Twist Bioscience.