Third generation autologous myeloid-derived dendritic cells developed from patients with CMML and MDS demonstrate phenotypic properties of mature functional dendritic cells

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders of the elderly characterized by inefficient haematopoiesis with frequent progression to AML. Chronic myelomonocytic leukaemia (CMML) is a clonal haematopoietic malignancy characterised by features of both MPN and MDS, including leukocytosis and monocytosis. It has poor prognosis and with the exception of allogeneic bone marrow transplantation no curative treatments options. Active immunotherapy (AIT) using dendritic cell (DC) vaccines have become an exciting concept for treating these patients. Our purpose was to find out (1) whether DCs generated from CMML and MDS patients acquire phenotypic and functional characteristics of mature DCs; (2) how many patients could be potential candidates for DC vaccine treatment taking in account their clinical characteristics and general condition. We investigated 10 CMML patients, 5 MDS patients and 5 healthy controls. Median age of CMML vs. MDS patients was 69 and 68. Mean monocyte count was 4,0x109/l and 1,0x109/l for CMML vs. MDS patients. Mean haemoglobin was 13 and 12 g/dl for CMML vs. MDS patients. Two CMML patients were previously treated with either HU or Aza, while all MDS patients were under active treatment at the time of sampling. All patients had ECOG status 0-1. DCs were developed by a novel protocol consisting of 2 days of culturing monocytes with GM-CSF and IL-4 followed by one day of maturation using GM-CSF, IL-4, TNF, INF-γ, PGE2, IL-1β and R848. We were able to generate mature functional DCs in 9/10 CMML cases and all MDS patients. There were insignificant variations in down-regulation of CD14 and expression of CD80, CD86, CD40, CD83, CD274, CCR7 and HLA-DR for patients compared to normal controls. Thus, all but one patient in the CMML group and all patients in MDS group could be relevant candidates for AIT with DC vaccine within a novel clinical protocol where DCs will be transfected with WT1 and PRAME mRNA.