We would like to comment on the article “Cost of decentralized CAR T cell production in an academic non-profit setting” by Ran et al1 published in your prestigious journal on June 14, 2020. This article touches a very sensitive topic which is currently under hot debate between chimeric antigen receptor (CAR) T-cell manufacturing University Hospitals and health care payers in Germany. We have produced almost 30 clinical-grade CD19-directed CAR T-cell products for our clinical trial within the last 2 years. These products were generated within an identical state and federal regulatory framework as anticipated by Ran et al for their model. However, our experience in terms of real-life financial effort for production of good manufacturing practice (GMP)-grade CAR T-cell products differs markedly from that calculated by the authors. These differences apply to all steps of production and clinical development as detailed in the following. Before use as standard of care, novel CAR T-cell products—similar to all drug innovations—have to be tested in clinical studies, putting an enormous additional financial burden on the product provider. These costs include but are not limited to complete clinical trial management, clinical research organization (CRO) costs, investigational product manufacturing, complying with all regulatory requirements, obtaining a multitude of approvals from national and state regulatory authorities, both for clinical trial performance and investigational product manufacturing, etc. In conclusion, the CART production cost estimates elaborated in the study by Ran et al grossly differ from real-world experience. Several costly aspects of CAR T-cell manufacturing for clinical use were not considered at all in the manuscript. Accordingly, is it possible that the authors simply calculated the costs for a research product and then added a gross estimate of regulatory costs? There is no doubt that scientific modeling has its value, but it needs to be validated by practical evidence and real-world application. In its present form, our study bears the risk of raising unrealistic expectations in the public and on the health care payer side. This may harm patients by impeding clinical development and application of academic CAR T-cell therapies. Michael Schmitt: Apogenix, Hexal and Novartis (research support). Hexal, Kite/Gilead (travel grants). Bluebird bio, Kite, Novartis (financial support for educational activities and conferences). MSD (advisory board member). MSD, GSK, Kite, BMS ([co-]PI of clinical trials). TolerogenixX Ltd. (co-founder and shareholder). Anita Schmitt: Hexal, Jazz Pharmaceuticals (travel grants). Therakos/Mallinckrodt (research grant). TolerogenixX Ltd. (co-founder, shareholder and part-time employee). Markus Thalheimer: none. Peter Dreger: Consultancy for AbbVie, AstraZeneca, Gilead, Janssen, Novartis, Riemser, Roche; speakers bureau for AbbVie, Gilead, Novartis, Riemser, Roche; research support from Neovii and Riemser. Carsten Müller-Tidow: Consultancy Advisory Board for Pfizer and Janssen, Grants and research support from Pfizer, Daiichi Sankyo, BiolineRx, Bayer AG.