Overcoming T cell tolerance to tumour antigens: an evaluation of the role of helper responses.

该项目旨在研究增强免疫系统的方法，以便能够根除癌细胞。我们将采取的策略是通过基因改变免疫细胞来识别癌细胞表面的分子。一旦被识别为异常，癌细胞应该被靶向杀死。然而，有时癌细胞和正常细胞之间的区别是不完整的。因此，免疫治疗的一个潜在问题是，修饰的免疫细胞可能会杀死正常细胞，导致“自身免疫”疾病。相反，它们可能无法识别癌细胞，或者受到过度刺激而停止杀伤。我们知道，有一些自然机制可以防止免疫细胞以这种方式变得无反应，例如在感染的情况下。也许我们可以利用这些，就像儿童疫苗使我们能够增强对常见病毒感染的免疫力一样。我们将在小鼠模型中研究基因改变的免疫细胞的功能。然后，我们将研究提高其识别和杀死癌细胞的策略，以期改善未来的癌症免疫疗法。

This project aims to investigate ways of enhancing the immune system such that it is able to eradicate cancerous cells. The strategy we will adopt is to genetically alter immune cells to recognise a molecule on the surface of cancer cells. Once recognised as abnormal, the cancer cell should be targeted for killing. However, sometimes the distinction between cancerous and normal cells is incomplete. A potential problem with immune therapy, therefore, is that modified immune cells may kill normal cells leading to ‘auto-immune‘ diseases. Conversely, they may either fail to recognise cancer cells or become over-stimulated and stop killing. We know that there are natural mechanisms which exist to prevent immune cells becoming unresponsive in this way e.g. in the setting of infection. It may be that we can exploit these, much as childhood vaccines have enabled us to boost immunity to common viral infectionsWe will investigate the functioning of genetically altered immune cells within a mouse model. We will then investigate strategies to improve their recognition and killing of cancer cells with a view to improving future immune therapies for cancer.