Anti-Thymocyte Globulin Kills Leukemic Stem Cells in Vitro

Background: Although curative treatment for acute myeloid leukemia, the success of allogeneic hematopoietic cell transplantation (HCT) is limited due to leukemia relapse and graft-versus-host disease (GvHD). Rabbit anti-thymocyte globulin (ATG) used for GvHD prophylaxis does not increase relapse (Walker et al: Lancet Oncol 2016). The non-increase in relapse could be because ATG has a direct anti-leukemic effect (Dabas et al: BBMT 2016). Multiple studies have suggested that a high number of leukemic stem cells (LSCs, also called leukemia initiating cells) remaining after therapy is associated with relapse. Therefore, targeting LSCs may be important for treating or preventing relapse. We demonstrated ATG's cytotoxic effect against acute myeloid leukemia (AML) blasts (Dabas et al: BBMT 2016). However, ATG's effect on LSCs has not been evaluated. In this study, we investigated in vitro ATG-induced complement-independent cytotoxicity (CIC, presumably direct induction of apoptosis) and complement-dependent cytotoxicity (CDC) against LSCs. This was also compared to ATG-induced CIC and CDC against healthy hematopoietic stem cells (HSCs).