Improving Chimeric Antigen Receptor (CAR) T-Cell Therapy Using Engineering Biology and Mechanobiological Approach

利用工程生物学和力学生物学方法改进嵌合抗原受体 (CAR) T 细胞疗法

• 批准号: 10074571
• 金额: $ 6.37万
• 依托单位: STEMBOND TECHNOLOGIES LTD
• 依托单位国家: 英国
• 项目类别: Grant for R&D
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=10074571
• 关键词: Improving; Chimeric; Antigen; Receptor; CAR

Why are cells not regularly used as medicine?If our cells repair us, keep us safe from pathogens and form our immune system, why do we not grow more in laboratories to help our bodies when needed?This is the basis of cell-based medicine: using cells to produce therapeutic products or to be transplanted into patients as therapy.One of the main applications of cell therapy today is cancer treatment. In this, the 'T cells' responsible for destroying cancers are transplanted to patients who need them. The concept is simple, but the execution is exceptionally difficult.The difficulty is keeping T cells 'happy' when taken from a patient or donor. As soon as cells leave the body, they begin to change, stop functioning as they should, and eventually, die.Biologists have typically used complex chemical environments to force cells to function and multiply in laboratory cultures. We now know, however, that the chemical environment is only half of the picture; cells must 'feel' that their mechanical environment is right for them. If we are to control the activation of T cells to multiply, their laboratory environment must have the same mechanical properties (such as stiffness) as naturally in a body.T cell activation and expansion are significant barriers to the cost-effective scaling of cell therapies, despite becoming a gold standard for many diseases, including cancer and arthritis.Cost-effective scaling and improved function of cell therapies can only be achieved through advanced engineering biology approaches.StemBond Technologies uses advanced material science to make cell culture environments that support optimal cell function. By controlling the mechanical environment of culture to optimise cell function, we will overcome the most significant obstacle to effective cell therapies. We will develop stiffness-modulatory microspheres to control T cell activation, increasing expansion yield, reducing cell exhaustion, and improving targeting.With this advancement, we will be one step closer to the routine use of cells as medicine.

为什么细胞不经常被用作药物？如果我们的细胞修复我们，让我们免受病原体的侵害，并形成我们的免疫系统，为什么我们不在实验室里培养更多的细胞，以便在需要时帮助我们的身体呢？这是细胞医学的基础：使用细胞生产治疗产品或将其移植到患者体内作为治疗。当今细胞疗法的主要应用之一是癌症治疗。在这种情况下，负责摧毁癌症的“T细胞”被移植到需要它们的患者身上。这个概念很简单，但执行起来却异常困难。困难在于从患者或捐赠者身上提取T细胞时要保持“快乐”。细胞一旦离开身体，它们就开始改变，停止应有的功能，最终死亡。生物学家通常使用复杂的化学环境来迫使细胞在实验室培养中发挥功能和繁殖。然而，我们现在知道，化学环境只是图片的一半;细胞必须“感觉”它们的机械环境适合它们。如果我们要控制T细胞的活化来繁殖，它们的实验室环境必须具有相同的机械性能T细胞活化和扩增是细胞疗法的成本有效扩展的显著障碍，尽管成为许多疾病的黄金标准，包括癌症和关节炎。成本-只有通过先进的工程生物学方法才能实现细胞疗法的有效扩展和改进功能。StemBond Technologies使用先进的材料科学，创造支持最佳细胞功能的细胞培养环境。通过控制培养的机械环境来优化细胞功能，我们将克服有效细胞疗法的最大障碍。我们将开发刚度调节微球，以控制T细胞活化，提高扩增产率，减少细胞耗竭，提高靶向性。随着这一进展，我们将更接近常规使用细胞作为药物。