BME PhD Prospectus Defense - Steve Wang

10:00 am on Wednesday, October 16, 2013
44 Cummington Mall, Room 203
Title: Development of a high-content functional T cell activation assay to characterize immunotherapy drug responses

Daniel Ehrlich, (Advisor/Chair)
Simon Kasif, BME
Wilson W. Wong, BME
Adrian Whitty, Chemistry

Modern cancer immunotherapy often involves the activation and proliferation of anti-tumor T cells to overcome immune tolerance, whether through the use of vaccination or adoptive transfer. However, there are strict biological limits against excessive T cell expansion, which is why immunotherapeutic agents are needed to overcome these limits. These agents, in combination with other therapies, have shown to enhance anti-tumor immune responses, but more often than not, result in weak clinical responses. Part of the reason is because the underlying mechanisms for these drugs are not fully understood and methods for measuring functional immune responses are lacking. In the following proposed research, I will develop a high content functional assay to understand the mechanism and efficacy of T cell based immunotherapies. The general approach involves tracking the spatial and temporal dynamics of T cell activation pathways in response to immunotherapeutic agents. This assay will leverage the high throughput and high content abilities of our 1D imaging parallel microfluidic cytometer (PMC) system. Because the PMC technology is still early in development, the first step involves improving and validating the hardware and fluidics. Novel statistical algorithms are being developed to correlate changes in 1D cell images to biological activity. Drug analogues of current immunotherapeutics will be screened and characterized for immune responsiveness. Finally, the assay will be adapted to primary peripheral blood T cells for maximum physiological relevance.