Antigen-specific co-stimulation to enhance the anti-tumour activity of TCR gene modified cytotoxic T lymphocytes

免疫系统可以保护个体免受病毒感染和某些类型肿瘤的生长。一些人类癌症是由病毒引起的，这使得免疫系统能够识别并消除病毒感染的癌细胞。免疫系统中的杀伤细胞对这种清除尤为重要，因为它们拥有受体分子，可以特异性地识别并杀死受感染的癌细胞。不幸的是，许多人类癌症不是由病毒感染引起的，因此不包含被杀伤细胞识别的病毒衍生标记。因此，杀伤细胞不能有效地识别和杀死这些癌细胞。在这个项目中，我们将对杀伤细胞进行基因修饰，使它们能够有效地识别人类癌细胞。我们将在杀伤细胞中引入编码两种受体的基因，这些受体特异性地识别存在于各种人类癌细胞中的标记物。通过这种方式，杀伤细胞可以使用两种受体并同时识别癌细胞中存在的两种标记物，这将导致有效的癌细胞杀伤。

The immune system can protect individuals against virus infection and against the growth of certain types of tumours. Some human cancers are caused by viruses, which allows the immune system to recognise and eliminate the virus-infected cancer cells. Killer cells of the immune system are particularly important for this elimination, as they possess receptor molecules that allow them to specifically recognise and kill infected cancer cells.Unfortunately, many human cancers are not caused by virus infection and therefore do not contain virus-derived markers that are recognised by killer cells. As a consequence, killer cells cannot efficiently recognise and kill such cancer cells. In this project we will gene modify killer cells such that they can efficiently recognise human cancer cells. We will introduce into killer cells the genes coding for two receptors that specifically recognise markers that are present in various human cancer cells. In this way, the killer cells can use two receptors and simultaneously recognise two markers present in cancer cells, which should result in efficient cancer cell killing.