The unpredictable and every-changing mapping of cancer as a disease means that significant research efforts have been dedicated to the discovery and development of new therapies. A recent shift to immunotherapies, due to greater efficacy and less taxing effects on the host, has resulted in the identification of Natural Killer (NK) cells as promising therapeutic agents. NK cells were initially proposed to offer a less toxic clinical alternative to Chimeric Antigen Receptor (CAR)-T therapies. However, in recent years, the application of novel multi-specific cell engagers has emerged for the harnessing of NK cell activation via targeting multiple activating receptors and by facilitating the formation of an immune synapse (IS) with tumour cells, whilst offering cytokine-induced increased NK cell proliferation.
A good understanding of cell-target interactions and signalling, and the harnessing of these, is key for a good therapeutic outcome. Nanomaterial-based therapeutics offer a strong potential in drug delivery and NK cell activation, due to their relative ease of functionalisation, good selectivity and targeting, and possibility to replicate the immune synapse and the nanoclustering seen in various mechanosensitive cellular interactions. The combination of nanomaterial and NK cell-based cancer therapies can enhance the efficacy of both, resulting in enhanced cytotoxicity and specificity, as well as a faster immune response.
In this thesis, nanographene oxide (NGO)-based nanomaterials are developed with the aim of exploiting two key features of NK cells – IS-induced molecular nanoclustering and the co-operative signalling of multiple immunoreceptors – to dramatically enhance NK cell activation. NGO-based sheets are biofunctionalised via a multi-step synthesis and then used to template molecular nanoclusters of monoclonal antibodies (mAb), with sizes of ~100 nm, and ~60...