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http://hdl.handle.net/11375/11245
Title: | The utilization of activated B cell for cell carrier for viral vectored antigen delivery in the acceleration of CD8 T cell recall response |
Authors: | Zhang, Liang |
Advisor: | Wan, Yonghong Brian Lichty, Jonathan Bramson Brian Lichty, Jonathan Bramson |
Department: | Medical Sciences (Molecular Virology and Immunology Program) |
Keywords: | cancer immunotherapy;cellular immunity;viral antigen delivery;Medical Immunology;Medical Immunology |
Publication Date: | Oct-2011 |
Abstract: | <p>Cancer vaccine therapy aims at harnessing effective antigen specific immune responses to treat tumor. In particular, CD8+ T cells have the unique capacity to recognize and destroy tumor cell throughout the body. One potential approach to elicit high numbers of effector CD8+ T cells to control tumor growth is through repeated vaccination, a strategy called prime-boost vaccination. However, booster immunization is relatively inefficient during primary immune response because pre-activated effector T cells tend to impair robust antigen presentation. This phenomenon has been interpreted as a negative feedback mechanism where recently activated CD8+ T cells clear the antigen-bearing dendritic cells (DCs) and prevent memory T cells from the access of the boosting antigen. Interestingly, however, using in vitro activated B cell as a viral vector delivery system, we can boost T cell responses with the minimum viral input at a very short interval between immunizations. This B cell carrier is capable of delivering different viral vectors expressing different antigens, displaying a potential for broad application. The mechanisms behind B cell carrier-mediated efficient secondary responses are three fold: 1. Without the engagement of MHC molecules and antigen presentation, B cell carrying viral vector can bypass the killing by pre-existing effector T cells 2. B cells can delivery viruses to B cell follicles, a place separated from effector T cells, and mediate memory T cell expansion. 3. B cells can deliver antigen to both spleen and lymph node and induce antigen specific T cell expansion in multiple lymphoid organs. Our studies provide a novel boosting platform to accelerate CTL responses that has important clinical implications.</p> |
URI: | http://hdl.handle.net/11375/11245 |
Identifier: | opendissertations/6227 7249 2251771 |
Appears in Collections: | Open Access Dissertations and Theses |
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