First published January 28, 2020 - More info
Background. Preclinical experiments have shown that donor blood cells, modified in vitro by an alkylating agent (MIC, modified immune cells), induced long-term specific immunosuppression against the allogeneic donor.
Methods. In this phase-I trial, patients received either 1.5x106 MIC per kg b.w. on day -2 (N=3, group A), or 1.5x108 MIC per kg b.w. on day -2 (N=3, group B) or day -7 (N=4, group C) before living donor kidney transplantation in addition to post-transplant immunosuppression. Primary outcome measure was the frequency of adverse events (AE) until day 30 (study phase) with follow-up to day 360.
Results. MIC infusions were extremely well tolerated. During the study phase, a total of 69 AE occurred in 10 treated patients which were unlikely/not related to MIC infusion. No donor-specific human leukocyte antigen antibodies or rejection episodes were noted even though the patients received up to 1.3x1010 of donor mononuclear cells prior to transplantation. Group C patients with low immunosuppression during follow-up showed no in vitro reactivity against stimulatory donor blood cells on day 360 while reactivity against third party cells was preserved. Frequencies of CD19+CD24highCD38high transitional B lymphocytes (Breg) increased from a median of 6% before MIC infusion to 20% on day 180, which was 19- and 68-fold higher, respectively, than in two independent cohorts of transplanted controls. The majority of Breg produced immunosuppressive cytokine IL-10. MIC-treated patients showed the Immune Tolerance Network operational tolerance signature.
Conclusion. MIC administration was safe and could be a future tool for the targeted induction of tolerogenic Breg.