Virus nanotechnology for intratumoural immunotherapy

Viruses can be designed to be tools and carrier vehicles for intratumoural immunotherapy. Their nanometre-scale size and shape allow for functionalization with or encapsulation of medical cargoes and tissue-specific ligands. Importantly, immunotherapies may particularly benefit from the inherent immunomodulatory properties of viruses. For example, mammalian viruses have already been tested for oncolytic virotherapy, and bacteriophages and plant viruses can be engineered for immunotherapeutic treatment approaches. In this Review, we discuss how viruses — including oncolytic viruses, immunomodulatory plant viruses and bacteriophages — and virus-like particles can be designed for intratumoural immunotherapy to elicit anti-tumour immunity and induce systemic anti-tumour responses at distant non-injected sites. We further highlight the engineering of viruses and virus-like particles as drug-delivery systems, and outline key translational challenges and clinical opportunities. Virus nanotechnology can be exploited for intratumoural immunotherapy. This Review discusses the clinical and preclinical landscape of viruses and virus-like particles as tools and carrier vehicles for intratumoural immunotherapy. Key points Viruses are immunomodulatory biologics that can be repurposed for intratumoural immunotherapy to kickstart the cancer immunity cycle. Mammalian viruses, non-mammalian viruses and virus-like particles can be engineered to trigger immune responses or deliver therapeutic cargo for immunotherapy. Virus-associated pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) recognition (through replication, nucleic acid payload, protein expression or structure) can induce type I interferon (IFN) responses and promote anti-tumour immunity. Intratumoural immunotherapy using virus-based nanomaterials and gene-delivery vectors benefit from low costs and dose requirements as well as minimal side-effects and systemic toxicity.