Comparing epitope preferences of full length and single domain antibodies

本项目将比较全长抗体和单结构域抗体结合位点的结构特征。大多数抗体治疗是单克隆抗体（mABs），包含整个Ig分子。尽管单克隆抗体在治疗方面取得了成功，但它们的高分子量会在生产过程中造成挑战，并导致组织穿透性降低。由于单克隆抗体中存在片段结晶区域，它们在患者中也可能过度免疫原性。这导致了对单域抗体及其衍生物的兴趣日益增加。单域抗体和全长抗体具有不同的生物物理特性，被认为在不同的情况下具有治疗作用。到目前为止，只有一种单域抗体被批准用于临床，但越来越多的抗体出现在临床试验中。这个项目的目的是利用现有的数据对粘合剂-目标，并使用这些信息来预测是否一个单一的结构域，或全长抗体将有效地针对一个给定的表位。这些信息将使我们在研究发现活动中的新蛋白质目标时选择适当的分子格式。最终，这将为我们提供最佳机会，使潜在候选药物的治疗效果最大化，从而增加其进入临床的机会。该项目属于EPSRC的“化学生物学和生物化学”研究领域，将与生物技术公司Twist Bioscience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.