The CMV-specific T cells were generated out of the patient’s own blood by grafting a well defined CMV-specific T cell receptor into the genomic locus of the endogenous TCR, a maneuvre termed orthotopic TCR replacement that had refined and advanced for clinical translation as part of the research program in the CRC338 LETSImmun. The patient’s T cells adopted the CMV-specific TCR like their own, and were able to regulate expression and signal strength such that they retained their fitness until all virus had been controlled, and then enter the memory T cell pool. The lead scientist had been a PhD-candidate and graduated in the first term of the CRC and now oversees a team of 10 scientists and engineers that cater enigneered lymphocyte products for patients with malignant, infectious and autoimmune diseases at the two major university hospitals in Munich. The team is well connected and integrated with the cell production facilities at other German university hospitals. The first product to be released at the production facility at the University Hospital in Würzburg on that day comprises T cells with immunosuppressive properties for a patient with type-I diabetes. The T cells have been enginneered with an optimized chimeric antigen receptor (CAR) that recognizes a molecule in the microenvironment of pancreatic islet cells. In that specific microenvironment, the T cells exert a regulatory function and interfere with the destructive immune-reaction that destroys the islet cells. Following this intervention, the patient can reduce and subsequently seize the administration of insulin – a disliked daily routine that had been with the patient for over 20 years since his childhood. The genetically engineered lymphocyte product had been developed by the CRC, and subsequently been developed by a biotech spinout that is still part of the CRC innovation ecosystem and cell therapy cluster that was established around the CRC to foster the clinical translation and development of novel cell therapy products. Already in the second funding period of the CRC, the number of IND filings that emerged from the cell therapy cluster for academic investigator initiated trials with gene-engineered lymphocytes had doubled compared to the number in 2020.