Catherine Bollard, M.D., Elizabeth Shpall, M.D. Baylor College of Medicine / University of Texas MD Anderson Cancer Center

TRANSPLANTATION/IMMUNE RECONSTITUTION

Ex vivo Expansion of Cord Blood Natural Killer cells for CLL Therapy

Grant Awarded in 2010

Abstract:

Allogeneic stem cell transplantation (SCT) is a potentially curative therapy for selected patients with chronic lymphocytic leukemia (CLL). However a significant proportion of patients – especially non-Caucasian patients - are unable to find a bone marrow donor for this life-saving treatment. Umbilical cord blood (CB) has emerged as an important donor source for these patients. CB can be procured quickly and requires less stringent “tissue type” matching when compared to unrelated bone marrow. Relapse following transplantation however remains a concern. One option to prevent relapse is to administer natural killer cells (NK) to CLL patients after transplant. NK cells made from adult blood have been given to leukemia patients after SCT with some good effects. However until now, CLL patients who received a CB transplant have not been able to be considered for NK cell therapy because the naïve NK cells in the CB unit are unable to kill tumor cells.

The central hypothesis of this proposal is that CB-derived NK cells can be manipulated in the laboratory to kill CLL. Furthermore we propose that NK cells can be expanded from CB to the numbers required for clinical use.  We aim to investigate the mechanism for the poor killing ability of CB NK cells and explore different techniques available in our laboratories to enable CB NK cells to kill CLL. The ultimate goal of this proposal is to optimize the conditions for the generation of CB-derived NK cells for a clinical trial that will study the effects of CB NK cells in CLL patients after CB transplant. Utilizing the unique expertise of each laboratory involved in this collaboration, the expansion and characterization of CB NK cells for clinical use will be performed at both the Baylor College of Medicine (Bollard) and MD Anderson Cancer Center (Shpall) sites.