Bioprocess Engineering for Therapeutic T-cell Manufacturing

新兴的培养细胞疗法具有治疗或治愈多种退行性和致命性疾病的潜力，目前正在进行数百项细胞免疫疗法临床试验。2017年批准的前两种免疫细胞（T细胞）疗法非常有效，可以治疗没有治疗选择的血细胞癌症。与使用化疗杀死癌细胞相反，这些T细胞免疫疗法是基于增强人体天然防御来杀死癌细胞。该提案的重点是产生T细胞，抑制其他免疫细胞追求错误的目标，如在移植排斥或自身免疫性疾病。这些细胞疗法可以取代免疫抑制药物的使用，这些药物通常是无效的，并且有许多副作用。虽然细胞免疫疗法有望彻底改变医学治疗，但必须克服许多挑战，使这些疗法成为许多需要它们的患者的现实。由于来自人类供体的T细胞的培养非常复杂，我们必须增加对用于产生这些治疗性细胞的过程的理解和控制。这是我们项目的重点。我们将提高治疗性细胞的产量，以便每个细胞供体都能治疗数百名患者。我们还寻求使网络加拿大的技能和资源，以促进临床试验。通过降低细胞生产成本和增加用于治疗的细胞数量，我们将有助于降低总体成本，使这些治疗在经济上对我们的医疗保健系统可行，并广泛用于挽救生命。我们对T细胞制造技术的开发将与加拿大细胞治疗制造设施系统地联网，以广泛地告知这种和其他依赖于细胞制造的有前途的临床治疗。

Emerging cultured cell therapies have the potential to treat or cure multiple degenerative and fatal diseases, and hundreds of cell immunotherapy clinical trials are currently underway. The first two immune cell (T-cell) therapies approved in 2017 are highly effective, and can treat blood-cell cancers for which no treatment options remained. In contrast to usingchemotherapy to kill cancer cells, these T-cell immunotherapies are based on amplifying natural human defences to kill cancer cells. This proposal is focussed on producing T cells that suppress other immune cells going after the wrong target, such as in transplant rejection or autoimmune disorders. These cell therapies could replace the use of immunosuppressivedrugs that are often ineffective and have many negative side effects. Although cell immunotherapy is poised to revolutionize medical treatments, many challenges must be overcome to make these therapies a reality for the many patients needing them. As the culture of T cells coming from human donors is very complex, we must increase our understanding and control of the processes used to produce these therapeutic cells. This is the focus of our project. We will improve the production of therapeutic cells so that hundreds of patients can be treated with each cell donor. We also seek to enable networked Canadian skills and resources to facilitate clinical trials. Through reducing the cell production costs and increasing the number of cells produced for treatment, we will contribute toward reducing overall costs, to make these treatments economically feasible for our healthcare system and widely available to save lives. Our development of T-cell manufacturing technology will be systematically networked with Canadian cell therapy manufacturing facilities to broadly inform this and other promising clinical treatments that depend on cell manufacturing.