Discussion
infection, premature death
MALIGNANCIES, EVENTS, INFECTION
We have recently shown that a single pretransplant infusion of MIC led to long-lasting donor-specific unresponsiveness (In our current analysis, none of the 10 MIC patients showed evidence of DSA against HLA-A, -B, -DR, or -DQB antigen mismatches during the 5-year follow-up period. The absence of DSA after but also on day -1 before transplantation is even more remarkable considering that MIC patients had received up to 1.34 x10Infections, malignancies, and cardiovascular events are the major causes of premature death in immunocompromised kidney transplant recipients (We admit that our study has limitations. We show 5-year follow-up of only 10 patients from a 30-day single-arm phase I clinical trial, and only 4 patients had received the highest MIC number 7 days before surgery, which was considered most effective. The 15 transplanted control patients were thoroughly matched but were selected retrospectively, and a potential selection bias toward better outcomes in MIC patients cannot be excluded. In addition, the control patients had basiliximab induction therapy and, because of the nature of the study, stronger immunosuppressive maintenance therapy, at least compared with MIC patients of group C. Another limitation arises from the fact that the anti-donor T-cell response and flow cytometry analyses were available only in MIC patients but not in transplanted controls. Nevertheless, the concomitant lower infection rates and a lower incidence of DSA in MIC patients suggest a potential clinical relevance of this cell therapy product when administered together with reduced conventional immunosuppressive therapy.In conclusion, MIC infusions prior to living donor kidney transplantation were shown in this small series to result in donor-specific unresponsiveness that effectively controls alloimmune responses. One would expect that this treatment would offer an opportunity to reduce the side effects of conventional chemical immunosuppression. These results are very promising and suggest that MIC therapy is a potential new effective treatment option for kidney transplant recipients. A Phase IIb study is currently underway to test the hypothesis that a larger series of patients treated with MIC and a reduced immunosuppressive drug regimen will show the same positive effects (EudraCT No. 2021-000561-33, ClinicalTrials.gov Identifier: NCT05365672) (