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Displaying Tetra‐Membrane Spanning Claudins on Enveloped Virus‐Like Particles for Cancer Immunotherapy
Author(s) -
Schneider Irene C.,
Hartmann Jessica,
Braun Gundula,
Stitz Jörn,
Klamp Thorsten,
Bihi Mahjoub,
Sahin Ugur,
Buchholz Christian J.
Publication year - 2018
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.201700345
Subject(s) - antigen , virology , antibody , biology , immunotherapy , cancer immunotherapy , virus like particle , vaccination , immune system , cytotoxicity , chemistry , immunology , gene , recombinant dna , biochemistry , in vitro
Virus‐like particles (VLPs) displaying foreign antigens have become an important tool in vaccination including the induction of immune responses against self‐antigens. Claudin 6 (CLDN6) has been identified as tumor‐associated antigen and is therefore a potential target for tumor vaccination strategies. However, as tetra‐membrane spanning protein its incorporation into VLPs while preserving a native fold is challenging. Here, we attempted the incorporation of a panel of engineered CLDN6 variants into the membrane of retrovirus‐derived VLPs. Interestingly, wild‐type CLDN6 revealed the most efficient display. VLPs presenting CLDN6 or CLDN9 derived from different donor species were produced and preservation of their native confirmation was demonstrated by antibody binding assays. VLPs displaying murine CLDN6 were used to immunize mice. Antibodies recognizing native CLDN6 as displayed on cell surfaces and mediating complement‐dependent cytotoxicity were elicited in vaccinated animals. The data suggest applications of CLDN6 displaying VLPs in cancer immunotherapy.