Read the full paper: Epitope Generation Gateway (EGG): A biological context-dependent approach to cancer vaccine development

The short-term and long-term effects of genotoxic pre-transplant conditioning remain barriers to the broader application of haematopoietic stem/progenitor cell (HSPC) transplantation and gene therapies1–4. Although monoclonal antibodies targeting KIT have been proposed as alternatives to chemotherapy or radiotherapy5–7, their pharmacokinetics hinder clinical applications owing to the risk of depleting transplanted HSPCs. Here, to address this issue, we identified amino acid changes in the extracellular domain of KIT that disrupt the binding of two therapeutic monoclonal antibodies8,9, which impair stem cell factor (SCF)-mediated signalling without affecting KIT expression or functionality. We exploited adenine base editing10 or prime editing11 to efficiently introduce these mutations in HSPCs and combined them with the disruption of the BCL11A erythroid enhancer to promote expression of fetal haemoglobin (HbF)12,13, a therapeutic approach for several haemoglobinopathies. This strategy

UCL Discovery is UCL's open access repository, showcasing and providing access to UCL research outputs from all UCL disciplines.

Crimean-Congo hemorrhagic fever is a severe, life-threatening, tick-borne disease with reported case-fatality rate of up to 40%. Recognized by the World Health Organization as a priority because of its epidemic potential in more than 30 countries, it lacks effective treatment, making the urgent development of a vaccine crucial. In this study, we employed a state-of-the-art immunoinformatics-driven approach to design a multi-epitope subunit vaccine targeting diverse Crimean-Congo hemorrhagic fever virus strains.

Epstein-Barr virus gp350 mediates viral attachment and is a leading vaccine target, yet its protective epitopes remain incompletely defined. Zhao et al. identify three distinct antibody-binding sites, including a neutralizing epitope outside the receptor-binding site, and show in vivo protection conferred by a fully human anti-gp350 monoclonal antibody.