Analysis of the clinical landscape for genetically-modified cellular immunotherapies highlights the need for optimized and consistent manufacturing processes

Abstract

Background & Aim Genetically-modified cellular immunotherapies, including chimeric antigen receptor T-cells (CAR-T) and natural killer cells (CAR-NK), have generated significant clinical and commercial outcomes due to their unparalleled response rates against cancer. However, the development and manufacture of these advanced therapies face a number of translational bottlenecks that must be addressed to ensure long-term commercial viability. Methods, Results & Conclusion A comprehensive analysis of the current clinical pipeline of genetically-modified cellular immunotherapies will be presented to demonstrate the implications of current manufacturing bottlenecks. This analysis will give a deeper understanding into future manufacturing process needs by highlighting clinical pipeline trends such as, autologous v. allogeneic or immune cell type utilized for therapy. The cost and variability associated with these personalized advanced therapies presents a critical manufacturing and translational challenge. The current clinical pipeline in this field shows the imminent need for manufacturing optimization. However, current manufacturing protocols vary widely, including media used, cytokine concentrations, and starting cell densities. This study will highlight the importance of determining critical manufacturing process parameters. The patient-specific nature of the CAR-T therapies currently on the market is a particular challenge for the field, therefore as much of the process must be controlled in order to decrease overall process variability.