Notice and Invitation
Oral Defense of Doctoral Dissertation
The Volgenau School of Engineering, George Mason University
Steven A. Roberts
Bachelor of Science, Clemson University, 2011
Liposome Mediated Expansion of T Cells for Immunotherapy
Tuesday, May 29, 2018, 10:00 am - 11:00 am
Engineering Building, Room 1602
All are invited to attend.
Committee
Dr. Nitin Agrawal
Dr. Juan R. Cebral
Dr. Fernando Mut
Dr. Ramin M. Hakami
Abstract
Adoptive cell therapy (ACT) is an evolving personalized cancer immunotherapy that has revolutionized contemporary cancer treatments. The approach has shown promising results in treating metastatic melanomas but has limited success
in other malignancies due to: 1) lack of cytotoxic T cells found during biopsies, 2) the difficulty and cost associated with genetically modifying and expanding small populations of T cells
ex vivo to therapeutic concentrations and 3) short term persistence of the inoculated T cells. To address these limitations, we hypothesized that liposomes can be used to deliver the T cell growth factor ‘IL-2’ directly to the cytotoxic T cells within
the body, thereby circumventing the need for ex vivo expansion and significantly reducing the associated costs and complexities. For my dissertation, I have characterized and validated this unique and novel approach
in vitro. First, a method for generating concentrated populations of small unilamellar liposomes is described. Following this, I demonstrate a novel approach for sequestering high concentrations of drugs within liposomes. Both of these techniques are
then utilized to encapsulate IL-2 and deliver the protein directly to CD-8+ T cells. Finally, microfluidic platforms offering the potential to directly observe the anticancer effect of activated t cells are developed and validated by observing the
real-time chemotaxis of cancer cells. This technology promises to improve and advance cancer immunotherapy and will eliminate many of the current limitations, ultimately leading to wider availability and implementation.