CombiVir: combinatorial engineering of therapeutic viruses

通过刺激病人自身的免疫系统来治疗癌症一直是一个白日梦。然而，最近的进展表明，两种新型疗法（检查点抑制剂药物和CAR-T细胞疗法）可以完全实现这一目标，尽管只适用于很小一部分患者，有时还会产生明显的副作用。受到这些结果的鼓舞，学术界和工业界都在迫切地寻求进一步的免疫疗法，以利用和扩展这些发现。溶瘤病毒免疫治疗（OVI）是一种非常有前途的治疗方法。肿瘤内病毒的选择性复制驱动肿瘤细胞死亡，导致癌症特异性抗原的释放。病毒在肿瘤中引发免疫反应，同时传递治疗有效载荷，刺激肿瘤内的免疫细胞。由于这些有效载荷仅在肿瘤内产生，因此不会产生目前在血液输注中显示的不良影响。在这里，我们使用合成生物学方法来设计一种新的基因表达病毒，该病毒充分利用牛痘病毒的独特特性，成为治疗癌症的破坏性技术。

Curing cancer though stimulation of a patient's own immune system has long been a pipedream. However, recent advances have shown that two novel classes of therapies (checkpoint inhibitor drugs; CAR-T cell therapy) can achieve exactly that, albeit in very small subsets of patients and with sometimes significant side-effects. Encouraged by these results a host of further immunotherapies are urgently being pursued, both academically and in industry, to capitalise and expand on these findings. One highly promising therapy is oncolytic virus immunotherapy (OVI). Selective replication of viruses within tumours drives tumour cell death leading to release of cancer-specific antigens. Viruses trigger an immune response in tumours while delivering therapeutic payloads that stimulate immune cells within the tumour. Because these payloads are only produced within the tumour they will not have the undesired effects they currently display upon bloodstream infusion. Here we use a synthetic biology approach to engineer a novel gene expressing virus that makes great use of unique characteristics of Vaccinia virus to become a disruptive technology in the treatment of cancer.