Dendritic cells (DCs) are promising mediators of anti-tumour immune responses. Unfortunately, a major hindrance to the development of highly effective DC vaccines is their short lifespan. Tumour antigen presentation may also not be optimal. We hypothesize that the introduction of exogenous survival factors (SFs) would prolong DC longevity and that modulation of TAA glycosylation will improve antigen presentation. To this end, we have constructed bicistronic lentivectors (LVs) encoding the xeno Tumour-Associated-Antigen (TAA), rHER-2/neu, and one of five candidate SFs. We demonstrated that our LVs can effectively protect transduced DCs from apoptosis when subjected to apoptosis-inducing conditions. TAA glycosylation has been proposed to obstruct the processing and presentation of peptides on MHC molecules. To address this second issue, we have engineered a LV that encodes a partially deglycosylated rHER-2/neu. Overall, we have generated the tools to alter intrinsic DC properties, which we believe will be integral to improving DC vaccine efficacy.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/25505 |
| Date | 30 December 2010 |
| Creators | Wang, James Chian-Ming |
| Contributors | Medin, Jeffrey A. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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