Safety of cell therapy products: in-vitro methods to assess the tumorigenicity of human cell-based therapeutic products

Background \u0026 Aim Human pluripotent stem cells (hPSCs) have the potential to revolutionize regenerative medicine. However, there are concerns associated with hES/iPSC-derived products, in particular, the possibility of residual undifferentiated PSCs persisting in the final product which could lead to tumorigenicity. Currently, there is no globally accepted consensus on the evaluation of methods for tumorigenicity in-vivo or in-vitro. This results in a high variability of data presented in regulatory submissions and difficulty in interpretations. To address this challenge, the Health and Environmental Sciences Institute (HESI) Cell Therapy-TRAcking, Circulation, \u0026 Safety (CT-TRACS) committee, convened international experts in the field, from multiple sectors and geographic areas, to critically review currently available in-vivo and in-vitro testing methods for tumorigenicity evaluation against expectations in international regulatory guidelines. The outcome of this effort was recently published in a position paper (Sato et al. 2019. Cytotherapy, 21: 1095–1111) and highlighted that the establishment of robust methods, internationally harmonized, for tumorigenicity assessment of cell therapy products is critically important not only for product developers but also for regulatory authorities and patients. Methods, Results \u0026 Conclusion Here we will present the follow-up activity of the committee: the launch of an international collaborative project to evaluate in-vitro testing methods focusing on the detection of residual undifferentiated PSCs using (1) ddPCR and (2) a highly efficient culture (HEC) assay. The two objectives for the multi-site study, among many, are to develop better, standardized in-vitro models for predicting tumorigenicity and to aid researchers, developers and regulators assess the safety of products with more confidence and contribute to faster/earlier decision-making. The initiative, open to organizations from the public and private sector, was announced and disseminated via a public call for participants. The intent is to generate transparent and reproducible data to inform decision making, support standards development, and ultimately develop methods to increase confidence in the safety assessment of hCTPs. HESI (www.hesiglobal.org) is an independent non-profit institution whose mission is to collaboratively identify and help to resolve global health and environmental challenges through the engagement of scientists from academia, government, industry, NGOs, and other strategic partners.