Improving T cell Functional Avidity through CD8 Co-receptor Modification: A Novel Mechanism to Enhance TCR Gene Therapy

通过 CD8 共受体修饰提高 T 细胞功能亲合力：增强 TCR 基因治疗的新机制

• 批准号: G0701311/1
• 负责人: Ignatius Chung Chua
• 金额: $ 35.08万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0701311%2F1
• 关键词: Improving; cell; Functional; Avidity; through

We are exploring a new approach to fight cancer. This involves re-programming part of the immune system known as T cells to kill cancer cells. This strategy involves transfering genes into T cells so that a protein known as TCR is expressed on the surface. The modified T cells target cancer cells and have been shown to eradicate tumour cells and prolong the survival of tumour bearing animals. Based on these results, we are about to start a clinical trial in patients with leukaemia.TCR require other molecules such as CD8 co-receptor to recognise tumour proteins. Both molecules need to associate closely in order for optimum function. By modifying CD8, we hope to increase the association and therefore the killing potential of the T cells. We will test our CD8 modified T cells in animal models.Part of this project will also look at how molecules interact on the surface of cells. Trying to visualise these molecules is challenging because they are so small. Advance microscopy techniques will be required to perform the imaging. The information obtained will give further insight on how to improve the function of modified T cells for cancer therapy.

我们正在探索一种抗击癌症的新方法。这涉及对免疫系统的一部分（称为 T 细胞）进行重新编程，以杀死癌细胞。该策略涉及将基因转移到 T 细胞中，以便在表面表达一种称为 TCR 的蛋白质。修饰后的 T 细胞以癌细胞为目标，并已被证明可以根除肿瘤细胞并延长荷瘤动物的存活时间。基于这些结果，我们即将开始针对白血病患者的临床试验。TCR需要其他分子如CD8共受体来识别肿瘤蛋白。两个分子需要紧密结合才能发挥最佳功能。通过修饰 CD8，我们希望增强 T 细胞的关联性，从而增强其杀伤潜力。我们将在动物模型中测试我们的 CD8 修饰 T 细胞。该项目的一部分还将研究分子如何在细胞表面相互作用。试图可视化这些分子是具有挑战性的，因为它们太小了。需要先进的显微镜技术来进行成像。获得的信息将进一步深入了解如何改善修饰 T 细胞的癌症治疗功能。