Date of Graduation
8-2015
Document Type
Thesis (MS)
Program Affiliation
Biomedical Sciences
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Scott Kopetz, MD, PhD
Committee Member
Elizabeth J. Shpall, MD
Committee Member
Muzaffar Qazilbash, MD
Committee Member
Patrick Hwu, MD
Committee Member
Laurence J. N. Cooper, MD, PhD
Abstract
Multiple myeloma (MM) is the second most common hematologic malignancy in adults and, to date, is incurable. Allogeneic natural killer (NK) cells are active in various hematologic malignancies and may have a role against MM. Umbilical cord blood is a potential source for allogeneic NK cells and ex vivo expanded umbilical cord blood-derived NK (CB-NK) cells demonstrate activity comparable to that of peripheral blood-derived NK cells. However, large-scale expansion of these cells is required for clinical translation. Here we studied a potential method for ex vivo expansion of NK cells from fresh and cryopreserved CB. Using artificial antigen presenting cells (aAPCs), interleukin-2 (IL-2) and a gas permeable culture system we were able to expand CB-NK cells 1848-fold (fresh CB) and 2389-fold (cryopreserved CB). The resultant cells were >95% pure for NK cells and demonstrated an activated, unexhausted phenotype. Expanded CB-NK cells demonstrated formation of functional immune synapses with target MM cells and dose-dependent cytotoxicity against various MM cell lines. Finally, infusion of CB-NK cells to a murine MM model resulted in slower progression of disease and improved survival. Thus CB-NK cells can be expanded to clinically meaningful doses for cellular therapy and may be an important immunotherapy tool to treat MM.
Keywords
Multiple myeloma, Natural killer cell, Cellular therapy, Ex vivo expansion