Automation in Hemopoietic Stem Cell Gene Therapy: Results of a Head-to-Head Comparison of a Manual Vs an Automated Procedure

The recent successes in gene therapy for the treatment of rare blood disorders such as primary immunodeficiencies and hemoglobinopathies have highlighted the need to generate robust and scalable manufacturing processes. Here we compare large scale lentiviral transductions of hemopoietic stem cells performed on the CliniMACS Prodigy^® to manual processes in terms of efficacy and viability of the end product. In our first series of experiments, we used a low, non-saturating MOI of 30 and the results showed that transduction efficiency on the CliniMACS Prodigy^® was significantly increased from an average of 23.3% (manual) to 50.5% (CliniMACS Prodigy^®). These results were further confirmed when we employed an MOI of 100 and showed that the average transduction efficiency was 74% from the CliniMACS Prodigy^® compared to 54.1% from the manual steps. Moreover, the total viability of the cells cultured on the CliniMACS Prodigy^® remained unaffected after two days of cultivation with an average recovery of 105% but with significantly less variability (SD: 15.4) compared to the manual steps (SD: 35.7). Finally there was no difference to the average VCN which was 2.2 from the manual steps and 2.4 from the CliniMACS Prodigy^®. Overall, our results indicate that the CliniMACS Prodigy^® generates higher transduction rates, combined with high viability compared to the manual process, but most importantly, with significantly lower variability, suggesting that it represents a closed system able to automatically perform complex processes as successfully as when manual handling steps are performed, but with higher predictability, efficiency and with minimal user interaction.