CombiVir: combinatorial engineering of therapeutic viruses

长期以来，通过刺激患者自身的免疫系统来治疗癌症一直是白日做梦。然而，最近的进展表明，两种新的疗法(检查点抑制剂药物；CAR-T细胞疗法)可以实现这一点，尽管在非常小的患者亚群中，有时还会有显著的副作用。在这些结果的鼓舞下，许多进一步的免疫疗法正在紧急地进行，无论是学术上还是工业上，以利用和扩大这些发现。一种非常有希望的治疗方法是溶瘤病毒免疫疗法(OVI)。肿瘤内病毒的选择性复制会导致肿瘤细胞死亡，从而导致癌症特异性抗原的释放。病毒在肿瘤中触发免疫反应，同时提供治疗有效载荷，刺激肿瘤内的免疫细胞。因为这些有效载荷只在肿瘤内产生，所以它们不会有目前在血液输注时表现出的不良影响。在这里，我们使用合成生物学的方法来设计一种新的基因表达病毒，它充分利用痘苗病毒的独特特性成为癌症治疗中的一项颠覆性技术。

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.