Synthetic carbohydrate ligands for immune receptors
One of the main challenges in the development of an effective anti-cancer vaccine is the generation of an adequate and directed cellular immune response.
- Reintjens, N.R.M.
- 27 February 2020
- Thesis in Leiden Repository
One of the main challenges in the development of an effective anti-cancer vaccine is the generation of an adequate and directed cellular immune response. Antigen presenting cells play an important role in obtaining such immune responses as they express pathogen recognition receptors (PRRs), for example Toll-like receptors (TLRs) and Nucleotide binding oligomerization domain (NOD)-like receptors (NLRs), and Fc receptors. This enables them to recognize pathogen associated molecular patterns (PAMPs). A promising strategy in immunotherapy is the use of PRR ligands or antibody-recruiting molecules (ARMs) that are covalently bound to an antigenic peptide. The research in this Thesis describes the design and synthesis of new carbohydrate ligands and conjugates for TLR4, NOD2 and mannose-6-phosphate receptor (MPR) in which these ligands are covalently bound to antigenic peptides. In the second part of this Thesis, Fc receptors are exploited as they bind to an immune complex, which is formed by binding of an antibody to an ARM. Therefore several C-glycosyl lysine building blocks are designed and synthesized of which C-rhamnose was conjugated several times to an antigenic peptide.