Abstract:
:Although the field of cancer immunotherapy is intensively investigated, there is still a need for generic strategies that allow easy, mild and efficient formulation of vaccine antigens. Here we report on a generic polymer-protein ligation strategy to formulate protein antigens into reversible polymeric conjugates for enhanced uptake by dendritic cells and presentation to CD8 T-cells. A N-hydroxypropylmethacrylamide (HPMA)-based copolymer was synthesized via RAFT polymerization followed by introduction of pyridyldisulfide moieties. To enhance ligation efficiency to ovalbumin, which is used as a model protein antigen, protected thiols were introduced onto lysine residues and deprotected in situ in the presence of the polymer. The ligation efficiency was compared for both the thiol-modified versus unmodified ovalbumin, and the reversibility was confirmed. Furthermore, the obtained nanoconjugates were tested in vitro for their interaction and association with dendritic cells, showing enhanced cellular uptake and antigen cross-presentation to CD8 T-cells.
journal_name
Biomacromoleculesjournal_title
Biomacromoleculesauthors
Lybaert L,Vanparijs N,Fierens K,Schuijs M,Nuhn L,Lambrecht BN,De Geest BGdoi
10.1021/acs.biomac.5b01571subject
Has Abstractpub_date
2016-03-14 00:00:00pages
874-81issue
3eissn
1525-7797issn
1526-4602journal_volume
17pub_type
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