Turning the tide: harnessing vaccines and viruses to fight cancer

Cancer vaccines and oncolytic viruses (OVs) represent promising immunotherapeutic strategies, harnessing adaptive and innate immune responses for targeted tumour eradication. Cancer vaccines aim to induce tumour-specific cytotoxic T lymphocytes (CTLs) through antigen presentation, while OVs mediate direct tumour lysis and stimulate immunogenic cell death, enhancing anti-tumour immunity. Despite keen interest, with over 350 clinical trials initiated since 2020, challenges persist in carrying the success seen in a pre-clinical setting to a clinical one. Advancements in preclinical modelling are essential for bridging the gap between <i>in vitro</i> findings and clinical efficacy. Traditional two-dimensional (2D) cultures, although cost-effective and reproducible, fail to recapitulate the complexity of the tumour microenvironment (TME). Three-dimensional (3D) models including spheroids, organoids, tumour-on-a-chip, and bioprinting offer improved architectural and physiological relevance, allowing for the assessment of immune cell infiltration and viral spread. <i>In silico</i> models further complement these systems by enabling high-throughput neoantigen prediction and therapy simulation. <i>In vivo</i> models such as patient-derived xenografts (PDXs), genetically engineered mouse models (GEMMs), and syngeneic models provide critical insights into tumour-immune dynamics and therapeutic efficacy in a systemic context at a whole organism level. Integrating 2D, 3D, <i>in silico</i>, and <i>in vivo</i> platforms provides a versatile basis for the preclinical evaluation of cancer vaccines and OVs. This multidisciplinary approach is vital to advancing personalized immunotherapies, improving biomarker development, and accelerating the translation of novel treatments.