Preclinical validation of a novel oncolytic viral therapy for multiple myeloma targeting readiness for clinical trials

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Multiple myeloma (MM) is an incurable blood cancer affecting ~5,800 UK citizens each year. Prognosis is poor with a <29% 10-year survival rate.MM treatments are given in cycles of triplet chemo-, immuno-, and corticosteroid- therapeutic combinations. Periods of remission between cycles become increasingly shorter (from 2+ years to <6-months) as the disease builds resistance, until eventual death. The primary limitation of existing treatments is their targeted approach, acting on a specific molecular site/pathway. MM has several defences to such therapies (genomic variability/heterogeneity, phenotypic plasticity/adaptability, and immune suppression/resistance).Whilst novel advanced therapies (CAR T-cell etc.) are emerging, these are also targeted in nature and unlikely to offer a durable treatment/cure.A further limitation of existing treatments is their cost (£50K-£200K/therapy, £200K+/combination treatment, and £800K+/patient across 4/5-treatment cycles).Oncolytic viruses (OVs) are an emerging therapy offering hope for difficult to treat cancers such as MM. OVs selectively infect/lyse/kill cancer cells, whilst simultaneously stimulating strong immune responses (lifting cancer-associated immune suppression). Importantly, OVs attack the cancer based on its phenotype rather than molecular targets. This enables high potency against systemic heterogeneous cancers (whilst preventing evolved resistance/immunity), providing durable remission/curative potential (and reduced treatment cycles).However, existing OVs are primarily re-purposed seroprevalent laboratory/wild-type viruses, not evolved/optimised for combating human cancers, and thus demonstrate limited efficacy/systemic stability. Furthermore, existing development approaches utilise laboratory cell lines/animal models that poorly reflect real tumour/human responses, frequently de-selecting viruses with efficacy in patients.Theolytics overcome these challenges through a novel OV Platform.