Scaling up the Manufacturing Process of Adoptive T Cell Immunotherapy

Adoptive T cell immunotherapy, involving the reprogramming of immune cells to target specific cancer or virus‐infected cells, has been recognized as a promising novel approach for the treatment of complex diseases. The impressive global momentum of this therapeutic approach has highlighted the urgent need for establishing it as an effective and standardized onco‐therapeutic approach in a large manufacturing scale. However, given its heterogeneity and uncertainty in nature, adoptive T cell immunotherapy is associated with a high failure rate that restricts its manufacturing to a limited number of institutions worldwide. It is undoubted that quite a few major challenges must be met before engineered T cells can be considered as a reliable, safe, and effective remedy for a broad range of diseases with global‐wise patient benefits. Here, the fundamental challenges that as yet remain unsolved in the manufacturing process before adoptive T cell therapy can be considered as a key element in the next generation of precision medicine is reviewed. It is proposed that it is necessary to adopt a closed system, automation, cost‐effective manufacturing model, and quality‐by‐design (QbD) strategy to enable scaled up manufacturing of adoptive T cell immunotherapy; and it is challenging to choose appropriate bioreactors, parameters, and infrastructure in this process. Standardizing the manufacturing process is of the ultimate importance for scaling up Adoptive Cell Therapy (ACT), where closed system, automation, cost‐effective manufacturing model, and quality‐by‐design are important strategies need to be adopted. Developing devices enabling automation is critical in standardizing the manufacturing process, where an integrated operation system allowing parallel processing of source cells in a high‐throughput fashion at a customizeable scale such as Cocoon offers a promising approach and will lead the field trend.