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Design of protein-reactive polymers and core-crosslinked nanoparticles in view of vaccine delivery

Nane Vanparijs (UGent)
(2016)
Author
Promoter
(UGent)
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Abstract
Delivering tumour-associated antigens (TAAg) to dendritic cells (DCs), the most potent class of antigen presenting cells (APCs) of our immune system, has emerged as a promising anti-cancer therapy by harnessing patients’ own immune system at recognizing and eliminating metastatic growth. Currently, several clinical trials obtain promising results with adoptive transfer of DCs and T cells that were conditioned ex vivo with TAAg. An even more viable approach is direct in vivo delivery of peptide- or protein-based TAAg to DCs in combination with specific immune-activating stimuli. The major bottleneck of this approach is the lack of efficiency of TAAg to provide DCs with the correct stimuli to steer the immune response towards the induction of cytotoxic T cells (CTLs) that can recognize and kill cancer cells. With respect to the improvement of CTL responses, molecular adjuvants have been developed that bind to pathogen recognition receptors (PRR) – such as Toll-like receptors (TLRs) – which are expressed on the cell surface or endosomal membrane of DCs. However, a major hurdle that hampers successful clinical translation of these components is the systemic inflammation caused when they enter systemic circulation. The aim of this thesis is the exploration of a materials chemistry approach to engineer the immune system by developing well-defined polymeric materials that can accommodate vaccine antigens and immune-modulatory components, and delivery these to DCs. From the materials chemistry side, efforts will focus on elucidating optimal conjugation strategies to link polymers to proteins, assemble proteins and polymers into nanoparticles, and formulate molecular adjuvants in polymeric nanoparticles. From the immunological side, efforts will focus on elucidating the in vitro and in vivo behaviour of the developed systems.

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Citation

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MLA
Vanparijs, Nane. Design of Protein-Reactive Polymers and Core-Crosslinked Nanoparticles in View of Vaccine Delivery. Ghent University. Faculty of Pharmaceutical Sciences, 2016.
APA
Vanparijs, N. (2016). Design of protein-reactive polymers and core-crosslinked nanoparticles in view of vaccine delivery. Ghent University. Faculty of Pharmaceutical Sciences, Ghent, Belgium.
Chicago author-date
Vanparijs, Nane. 2016. “Design of Protein-Reactive Polymers and Core-Crosslinked Nanoparticles in View of Vaccine Delivery.” Ghent, Belgium: Ghent University. Faculty of Pharmaceutical Sciences.
Chicago author-date (all authors)
Vanparijs, Nane. 2016. “Design of Protein-Reactive Polymers and Core-Crosslinked Nanoparticles in View of Vaccine Delivery.” Ghent, Belgium: Ghent University. Faculty of Pharmaceutical Sciences.
Vancouver
1.
Vanparijs N. Design of protein-reactive polymers and core-crosslinked nanoparticles in view of vaccine delivery. [Ghent, Belgium]: Ghent University. Faculty of Pharmaceutical Sciences; 2016.
IEEE
[1]
N. Vanparijs, “Design of protein-reactive polymers and core-crosslinked nanoparticles in view of vaccine delivery,” Ghent University. Faculty of Pharmaceutical Sciences, Ghent, Belgium, 2016.
@phdthesis{8130348,
  abstract     = {Delivering tumour-associated antigens (TAAg) to dendritic cells (DCs), the most potent class of antigen presenting cells (APCs) of our immune system, has emerged as a promising anti-cancer therapy by harnessing patients’ own immune system at recognizing and eliminating metastatic growth. Currently, several clinical trials obtain promising results with adoptive transfer of DCs and T cells that were conditioned ex vivo with TAAg. An even more viable approach is direct in vivo delivery of peptide- or protein-based TAAg to DCs in combination with specific immune-activating stimuli. The major bottleneck of this approach is the lack of efficiency of TAAg to provide DCs with the correct stimuli to steer the immune response towards the induction of cytotoxic T cells (CTLs) that can recognize and kill cancer cells. With respect to the improvement of CTL responses, molecular adjuvants have been developed that bind to pathogen recognition receptors (PRR) – such as Toll-like receptors (TLRs) – which are expressed on the cell surface or endosomal membrane of DCs. However, a major hurdle that hampers successful clinical translation of these components is the systemic inflammation caused when they enter systemic circulation. 
The aim of this thesis is the exploration of a materials chemistry approach to engineer the immune system by developing well-defined polymeric materials that can accommodate vaccine antigens and immune-modulatory components, and delivery these to DCs. From the materials chemistry side, efforts will focus on elucidating optimal conjugation strategies to link polymers to proteins, assemble proteins and polymers into nanoparticles, and formulate molecular adjuvants in polymeric nanoparticles. From the immunological side, efforts will focus on elucidating the in vitro and in vivo behaviour of the developed systems.},
  author       = {Vanparijs, Nane},
  language     = {eng},
  pages        = {247},
  publisher    = {Ghent University. Faculty of Pharmaceutical Sciences},
  school       = {Ghent University},
  title        = {Design of protein-reactive polymers and core-crosslinked nanoparticles in view of vaccine delivery},
  year         = {2016},
}