Converting iPSC to T Cells: Key Challenges and Considerations
Chimeric antigen receptor (CAR)-engineered T cells (CAR-T) have been remarkably successful in clinical treatment of relapsed or refractory haematological tumours such as B-cell acute lymphoblastic leukaemia (ALL), lymphomas and Multiple Myeloma1. Human induced pluripotent stem cells (iPSCs) are now poised to revolutionize the field of CAR-T immune cell therapy by offering a platform that can (a) be uniformly genetically engineered for allogeneic cell therapy and (b) offers a potentially unlimited source of T-cells for therapeutic applications2, that can help meet the increasing patient demand and clinical indications treatable by CAR-T3.
One of the key challenges in iPSC-based cell therapy is the controlled and efficient differentiation of iPSCs into specific cell lineages, particularly T-cells and their diverse sub-types (e.g., γδ T-cells, αβ CD4 or CD8 T-cells) (Figure 1, 4). Thus, the success of iPSC-based allogeneic cell therapies relies heavily on a comprehensive understanding of developmental and pluripotent stem cell biology and the ability to translate this to a robust cGMP manufacturing process.
This article explores the biological considerations involved in iPSC differentiation, with a specific focus on generating T-cells for cell therapy.
