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.