The recent successes of CAR T cell therapy in fighting hematologic malignancies have led to tremendous interest in the immunotherapeutic field, whilst the great potential of genetically modified T cells now expands into solid tumors and infectious diseases. However, the manufacturing processes used for engineering T cells consist of various complex procedures, are labor intensive, and represent some of the biggest challenges in this area. This article will describe the CliniMACS Prodigy® Platform and the new associated T Cell Transduction—Large Scale (TCT–LS) process, and present data from CD8+ TCR-modified T cell engineering in the setting of acute myeloid leukemia. Process details and differentiators will be shared, along with limitations and how to choose the right process type for your requirements.