Control of immune response in an iPSC-based allogeneic cell therapy clinical trial for Parkinson’s disease

Because the central nervous system (CNS) is an immune-privileged organ, it requires different immunosuppression strategies for cell therapies using induced pluripotent stem cells (iPSCs) compared with ones for organ transplantations. We recently conducted the first in-human clinical trial of a cell therapy for Parkinson’s disease using allogeneic iPSCs (jRCT number: jRCT2090220384). All patients were transplanted with dopaminergic neural progenitors differentiated from iPSCs (iPSC-DANs), which had homozygous human leukocyte antigen (HLA) haplotypes, through immunosuppression with tacrolimus alone. No clinically significant immune reaction was observed in this study, regardless of HLA compatibility. However, a highly sensitive mixed lymphocyte reaction using iPSC-derived dendritic cells as a stimulator demonstrated the activation of lymphocytes from HLA-mismatch-grafted recipients. This finding suggests that the low expression of HLA in iPSC-DANs contributes to successful engraftment in the immune-privileged CNS. These results indicate that only moderate immunosuppressive treatment may be required for stem cell transplantation to the CNS. • Tacrolimus alone was used for immunosuppression in the trial • No clinical immune reaction was observed, regardless of HLA compatibility • Conventional immunosuppression may be reduced in CNS stem cell therapies • MLR using iPSC-dendritic cells (DCs) indicated a higher risk in HLA mismatch Morizane et al. reported on the immune responses observed in an allogeneic iPSC-based cell therapy trial for Parkinson’s disease. A milder immunosuppressive regimen, compared with those used in organ or fetal ventral mesencephalon transplants, effectively managed the immune response to the grafted iPSC-dopamine neurons (DANs).