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

针对多发性骨髓瘤的新型溶瘤病毒疗法的临床前验证，为临床试验做好准备

• 批准号: 10017183
• 金额: $ 100.11万
• 依托单位: THEOLYTICS LTD
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10017183
• 关键词: Preclinical; validation; novel; oncolytic; viral

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.

多发性骨髓瘤（MM）是一种无法治愈的血癌，每年影响约5，800名英国公民。预后差，10年生存率<29%。MM治疗以三联化疗、免疫和皮质类固醇治疗组合的周期给予。随着疾病建立抵抗力，周期之间的缓解期变得越来越短（从2年以上到<6个月），直到最终死亡。现有治疗的主要限制是它们的靶向方法，作用于特定的分子位点/途径。MM对此类疗法具有几种防御（基因组变异性/异质性、表型可塑性/适应性和免疫抑制/抗性）。这些方法在本质上也是有针对性的，不太可能提供持久的治疗/治愈。现有治疗的另一个限制是它们的成本（£ 50 K-£ 200 K/疗法，£ 200 K +/组合治疗，和£ 800 K +/患者跨越4/5治疗周期）。溶瘤病毒（OV）是一种新兴疗法，为难以治疗的癌症如MM提供了希望。OV选择性地感染/裂解/杀死癌细胞，同时刺激强烈的免疫反应（解除癌症相关的免疫抑制）。重要的是，OV基于其表型而不是分子靶标来攻击癌症。这使得能够针对系统性异质性癌症（同时防止进化的抗性/免疫）具有高效力，提供持久的缓解/治愈潜力（和减少的治疗周期）然而，现有的OV主要是重新利用的血清阳性实验室/野生型病毒，没有进化/优化用于对抗人类癌症，因此表现出有限的功效/系统稳定性。此外，现有的开发方法利用的实验室细胞系/动物模型不能很好地反映真实的肿瘤/人类反应，经常对患者有效的病毒进行去选择。Theolytics通过新的OV平台克服了这些挑战。