Affiliation:
1. Dept. Materials Imperial College London Exhibition Road London SW7 2AZ UK
2. Dept. Life Sciences Imperial College London Exhibition Road London SW7 2AZ UK
3. Dept. Chemistry Imperial College London Molecular Sciences Research Hub London W12 0BZ UK
Abstract
AbstractMany emerging cancer treatments are immunotherapies that modulate Natural Killer‐ (NK) or T cell activation, posing a challenge to develop immunoengineering nanomaterials that improve on the performance of molecular reagents. In physiological activation, multiple immunoreceptors signal in consort; however, current biomaterials do not replicate this. Here, NK cells are created for the first time, activating bionanomaterials that stimulate >2 immunoreceptors. Nanoclusters of monoclonal antibodies (mAb), templated by nanoscale graphene oxide sheets (NGO) (≈75 nm size), are exploited. To inform nanoreagent design, a model system of planar substrates with anchored mAb is first investigated. Combining mAb that stimulates three NK cell activating receptors (αNKP46 + αNKG2D + αDNAM‐1), activated NK cells act more potently than any single receptor or pair. Applying this insight, an NGO‐mAb nanocluster combining three distinct mAb: NGO‐mAb(αNKP46 + αNKG2D + αDNAM‐1) is created. This construct is potent and outperforms single‐receptor‐simulating nanoclusters, activating nearly twice as many NK cells as NGO‐mAb(αNKP46) at a similar mAb dose or delivering similar activation at 10× lower dosage. Further, NGO‐mAb are more potent than planar substrates for both single‐ and triple‐mAb stimulation. These results imply a new concept for immunoengineering biomaterials: both nanoclustering and multi‐receptor stimulation should be incorporated for maximum effect.
Funder
Engineering and Physical Sciences Research Council
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials