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Exploring the effects of nutrient deprivation on T cells and oncolytic adenoviruses, in order to create immune activators for tumour therapy

探索营养剥夺对 T 细胞和溶瘤腺病毒的影响，以创造用于肿瘤治疗的免疫激活剂

基本信息

批准号：
1813152
负责人：
金额：
--
依托单位：
University of Oxford
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1813152
关键词：
Exploring effects nutrient deprivation cells

项目摘要

Oncolytic viruses can replicate selectively within the tumour microenvironment and kill tumour cells, before spreading to infect adjacent cells. They can kill cells directly and can also encode potent biologicals for selective expression within tumours. However, viruses must be able to produce multiple copies of themselves under the challenging nutrient-restricted and acidic environment of solid tumours. This project will explore the interface between adenovirus activity and the limitation of amino acid supply within tumours, for example mediated by over-expression of the enzyme IDO which breaks down local tryptophan. It will also cover adenovirus activity under acidic conditions found to be in solid tumours. The work should go on to then monitor the resulting environment following virus infection and how this may affect long term changes in the tumour, for example the activity of immune cells, specifically T cells following oncolytic viral infection. The project will be at the interface of basic biology and therapeutic development and will make use of many techniques including molecular cloning as well as virology and cell culture techniques.

溶瘤病毒可以在肿瘤微环境中选择性复制，杀死肿瘤细胞，然后扩散到感染邻近细胞。它们可以直接杀死细胞，也可以编码有效的生物制品，在肿瘤内选择性表达。然而，病毒必须能够在具有挑战性的营养限制和固体肿瘤的酸性环境中产生自己的多个副本。这个项目将探索腺病毒活性和肿瘤内氨基酸供应限制之间的接口，例如通过过度表达IDO酶来分解局部色氨酸。它还将复盖腺病毒在酸性条件下的活性，发现在固体肿瘤中。这项工作应该继续监测病毒感染后产生的环境，以及这可能如何影响肿瘤的长期变化，例如免疫细胞的活动，特别是溶瘤病毒感染后的T细胞。该项目将处于基础生物学和治疗开发的交界处，并将利用许多技术，包括分子克隆以及病毒学和细胞培养技术。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Bi- and tri-valent T cell engagers deplete tumour-associated macrophages in cancer patient samples

DOI：
10.1186/s40425-019-0807-6
发表时间：
2019-11
期刊：
Journal for Immunotherapy of Cancer
影响因子：
10.9
作者：
Eleanor M Scott;Egon J. Jacobus;B. Lyons;Sally Frost;Joshua D Freedman;A. Dyer;H. Khalique;
通讯作者：
Eleanor M Scott;Egon J. Jacobus;B. Lyons;Sally Frost;Joshua D Freedman;A. Dyer;H. Khalique;

Use of Liquid Patient Ascites Fluids as a Preclinical Model for Oncolytic Virus Activity.

使用液体患者腹水作为溶瘤病毒活性的临床前模型。