Combination immunotherapy for solid tumours with oncolytic virus & cognate CAR T-cells

在英国，每年大约有35万新确诊的癌症病例。尽管采用了现代治疗方法，但许多患者仍无法治愈。最近利用免疫系统抗击癌症的科学发现正在改变一小部分患者的生活。不幸的是，大多数晚期癌症患者从这种方法中获益微乎其微。该项目旨在测试一种创新策略，以增强人体对抗各种癌症的能力。由于这一策略是新的，在开发用于人体试验之前，在培养皿中培养的细胞和小鼠身上测试它的安全性和有效性是至关重要的。从本质上讲，这是一个由两部分组成的项目，使用尖端基因工程来实现其目标。这个想法是设计一种只会感染癌细胞的病毒。一旦进入体内，人们希望这种病毒可以使癌细胞容易受到称为T细胞的杀伤性白血球的攻击。这些T细胞是我们免疫系统的重要组成部分，也将通过基因工程来寻找和杀死癌细胞。该病毒还将被设计为产生一种化学物质，可以增强肿瘤对免疫攻击的敏感性。T细胞的进一步工程化也可能被用来改进它们靶向肿瘤的方式。由于实验的设计方式，人们希望在未来，这一策略可以应用于大量患有多种不同类型癌症的患者。人们还希望，通过对病毒和T细胞进行额外的改变，以增强治疗方法根除肿瘤的能力，这项研究的基本想法可以进一步推进。

Every year approximately 350,000 new cases of cancer are diagnosed in the UK. Despite modern treatments many patients cannot be cured. Recent scientific discoveries harnessing the immune system to fight cancer are transforming the lives of a small group of patients. Unfortunately, the majority of patients with advanced cancer gain minimal benefit from this approach. This project aims to test an innovative strategy that could enhance the body's ability to fight various cancers. Because the strategy is new, it is vital to test how safe and effective it is in cells grown in a dish and in mice before it is developed for use in human trials. Essentially, it is a project of two halves, using cutting-edge genetic engineering to achieve its goals. The idea is to engineer a virus that will only infect cancer cells. Once inside it is hoped that the virus can render the cancer cells susceptible to attack by killer white blood cells called T-cells. These T-cells, which form an important part of our immune system, would also be genetically engineered to seek out and kill cancer cells. The virus would also be designed to produce a chemical that can enhance the susceptibility of the tumour to immune attack. Further engineering of the T-cells may also be used to improve the way in which they can target tumours. Because of the way in which the experiments are designed, it is hoped that in the future this strategy can be applied to a very large number of patients with many different types of cancer. It is also hoped that the idea underlying the research can be further advanced by making additional changes to both the virus and the T-cell to enhance the treatment's ability to eradicate tumours.