Chimeric antigen receptor T-cell (CAR-T) therapies have emerged as a revolutionary approach in the field of hematological malignancies, offering unprecedented clinical efficacy when patients have exhausted any other treatment option. Currently, six CAR-T products are available worldwide, but many of the manufacturing challenges are yet to be addressed. In addition, a single therapeutic dose of CAR-T can cost up to USD 500K. A significant fraction of the cost is related to manufacturing the viral vector required to introduce the clinically relevant CAR construct. As such, non-viral gene delivery platforms such as electroporation or mechanoporation can potentially decrease the costs of manufacturing associated with CAR-T products. This study focused on establishing a scalable manufacturing method for CAR-T cell therapies using electroporation and a sleeping beauty transposon-transposase system employed to ensure stable integration of the CAR transgene.

Learning Objectives: 

1. Review what chimeric antigen receptor (CAR) T cell therapies are and how they are manufactured.

2. Demonstrate knowledge on the manufacturing process and which unit operations are in urgent need of optimisation to achieve cost reduction. 

3. Develop fundamental knowledge on how non-viral technologies can be used for knock-in and knock-out certain genes within the CAR-T manufacturing context.