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

为什么细胞不经常被用作药物？如果我们的细胞修复我们，保护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来帮助我们的身体在需要的时候？这是细胞医学的基础：利用细胞生产治疗产品或将其移植到患者体内作为治疗。目前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。难点在于如何保证从病人或捐赠者身上提取的T细胞“正常运转”。一旦细胞离开身体，它们就开始发生变化，停止发挥应有的功能，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作用和繁殖。然而，我们现在知道，化学环境只是问题的一半；细胞必须“感觉到”它们的机械环境是适合它们的。如果我们要控制T细胞的激活繁殖，它们的实验室环境必须具有与人体自然环境相同的机械特性（如硬度）。尽管T细胞活化和扩增已成为治疗包括癌症和关节炎在内的许多疾病的黄金标准，但它仍是成本效益扩大细胞疗法的重大障碍。只有通过先进的工程生物学方法，才能实现具有成本效益的细胞疗法的规模化和功能的改进。StemBond技术使用先进的材料科学，使细胞培养环境，支持最佳的细胞功能。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治疗的最大障碍。我们将开发刚度调节微球来控制T细胞活化，增加扩增量，减少细胞耗竭，提高靶向性。有了这一进展，我们离将细胞作为常规药物又近了一步。

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.