Improving nanobodies’ affinity via chemical mutagenesis
Cancer immunotherapy has emerged as one of the best alternatives to current chemotherapy treatments. Nanobodies (VHH antibodies) are antibodies with a single variable domain located on a heavy chain. Conventional antibodies have VH and VL variable domains, which provide stability and binding specificity. Nanobodies have VHH domains and lack VL domains and occur naturally in camelids and sharks. Nanobodies have found use in such medical fields as oncology, infection and immunity. The EU-funded Chemical Mutagenesis project proposes the development of nanobodies able to recognise HER-2 protein and PD-1 receptors in cancer cells. The objective is to improve the nanobodies’ affinity to their targets using chemical mutagenesis via alanyl radicals, with a goal of resolving the challenges of cancer resistance in the context of immunotherapy.