Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Safety and Preliminary Efficacy of Mesenchymal Stromal Cell (ORBCEL-M Cell) Therapy in Diabetic Kidney Disease: A Randomized Clinical Trial (NEPHSTROM).

Abstract

BACKGROUND: Systemic therapy with mesenchymal stromal cells (MSCs) may target maladaptive processes involved in diabetic kidney disease (DKD) progression. However, clinical translation of this approach has been limited. METHODS: The Novel Stromal Cell Therapy for Diabetic Kidney Disease (NEPHSTROM) study, a randomized, placebo-controlled phase 1b/2a trial, assesses safety, tolerability, and preliminary efficacy of next-generation bone marrow-derived, anti-CD362-selected, allogeneic MSCs (ORBCEL-M) in adults with type 2 diabetes and progressive DKD. This first, lowest-dose cohort of 16 patients at three European sites was randomized (3:1) to receive intravenous infusion of ORBCEL-M (80 x 106 cells, n=12) or placebo (n=4) and followed for 18 months. RESULTS: At baseline, all participants were negative for anti-HLA antibodies and the measured glomerular filtration rate (mGFR) and estimated GFR (eGFR) were comparable between groups. The intervention was safe and well tolerated. One placebo-treated patient had a quickly resolved infusion reaction (bronchospasm), with no subsequent treatment-related serious adverse events. Two ORBCEL-M recipients died during follow-up of causes deemed unrelated to the trial intervention; one recipient developed low-level anti-HLA antibodies. The median annual rate of kidney function decline following ORBCEL-M compared with placebo did not differ by mGFR but was significantly lower by eGFR estimated by the CKD-EPI and MDRD equations. Immunologic profiling provided evidence of preservation of circulating regulatory T cells, lower natural killer T cells, and stabilization of inflammatory monocyte subsets in those receiving the cell therapy compared with placebo. CONCLUSIONS: Findings indicate safety and tolerability of intravenous ORBCEL-M cell therapy in the trial's lowest-dose cohort. The rate of decline in eGFR (but not mGFR) over 18 months was significantly lower among those receiving cell therapy compared with placebo. Further studies will be needed to determine the therapy's effect on CKD progression.