Mgta-456 Contains Large Numbers of CD34+CD90+ Hematopoietic Stem Cells (HSC) Which Contain the NSG Engraftment Activity and Correlate with Time to Neutrophil Recovery Following Transplant into Patients with Hematologic Malignancy

Background Patient access to well-matched cord blood (CB) containing high doses of stem cells remains a challenge for successful transplants. Low numbers of CD34+ cells in CB has resulted in delayed neutrophil recovery and increased risk of graft failure. MGTA-456 is a cell therapy that consists of CD34+ cells expanded in a 15-day culture in the presence of an aryl hydrocarbon receptor antagonist (AHRa) and the CD34 depleted fraction obtained from the same CB unit. To date, 41 patients with hematological malignancies (n=36) and non-malignant diseases (n=5) have received MGTA-456 with a median follow-up of 2.5 years (range 0.1 to 5 years) and 75 days (80 to 203 days), respectively. All patients engrafted at a significantly faster rate as compared to similarly treated historical controls (p Results After the selected CD34+ cells are cultured, the expanded product is ∼35% CD34+ and 65% CD34- (Figure 1). The CD34+ cells can be further fractionated into CD34+CD133-CD90- cells (late progenitors), CD34+CD133+CD90- cells (early progenitors) and CD34+CD133+CD90+ (progenitors and stem cells) as shown in Figure 1. The CD34- cells within the expanded product contained erythroid (CD71+) and megakaryocyte progenitors (CD41+), CD33+, CD14+, CD15+, and CD11b+ myeloid cells and CD56+ cells. CD3+, CD8+, CD4+, CD16+, CD19+ as well as CD10+ cells were not present ( Conclusion In these studies, we demonstrate that the expanded CD34+ cell fraction of MGTA-456 contains large numbers of CD34+CD90+ HSC, which are critical for long term engraftment in NSG mice and correlated with rapid neutrophil recovery clinically.