Rate of immune reconstitution (IR) directly correlates with the number of hematopoietic stem cells (HSC) infused and is particularly delayed in patients undergoing cord blood (CB) transplantation (CBT). Methods to increase the number of CB progenitors have the potential to accelerate IR after CBT. NK cells are the first lymphocyte subset to recover after HSC transplant (HCT) and are crucial in preventing early relapse. Unfortunately, NK cells in CB are low in number, incomplete in maturation and require activation for effective function. Here, we report a clinically relevant ex vivo expansion method that optimizes maturation as well as activation of CB NK cells. CB NK cells cultured 14-21 days with CB mononuclear cells, IL-2 and IL-15 result in a multi-log increase in cell number. Potential killer cell Ig-like receptor (KIR) ligand and adhesion molecule(s) responsible for NK cell cytotoxicity were examined prior to and after culture. Phenotypic analysis showed that the percent of NK cells expressing activating receptors and adhesion molecules increased (CD336 +39.11%) while inhibitory receptor expression decreased (CD159a -25.09%). Furthermore, cytotoxic function of CB NK cells against NK cell sensitive (K562) and resistant (MV4-11) cancer cells lines were enhanced after culture. The data suggest that this ex vivo expansion method of matured and activated NK cells is a potential clinically relevant method to prevent early relapse after CBT.
- Copyright © 2013 by The American Association of Immunologists, Inc.