Encapsulation in liposomal nanoparticles enhances the immunostimulatory,adjuvant and anti-tumor activity of subcutaneously administered CpG ODN |
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Authors: | Susan de Jong Ghania Chikh Laura Sekirov Sam Raney Sean Semple Sandra Klimuk Ning Yuan Micheal Hope Pieter Cullis Ying Tam |
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Institution: | (1) Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada;(2) Inex Pharmaceuticals Corporation, Burnaby, BC, Canada |
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Abstract: | Immunostimulatory oligodeoxynucleotides (ODN) containing cytosine-guanine (CpG) motifs are powerful stimulators of innate
as well as adaptive immune responses, exerting their activity through triggering of the Toll-like receptor 9. We have previously
shown that encapsulation in liposomal nanoparticles (LN) enhances the immunostimulatory activity of CpG ODN (LN-CpG ODN) (Mui
et al. in J Pharmacol Exp Ther 298:1185, 2001). In this work we investigate the effect of encapsulation on the immunopotency of subcutaneously (s.c.) administered CpG
ODN with regard to activation of innate immune cells as well as its ability to act as a vaccine adjuvant with tumor-associated
antigens (TAAs) to induce antigen (Ag)-specific, adaptive responses and anti-tumor activity in murine models. It is shown
that encapsulation specifically targets CpG ODN for uptake by immune cells. This may provide the basis, at least in part,
for the significantly enhanced immunostimulatory activity of LN-CpG ODN, inducing potent innate (as judged by immune cell
activation and plasma cytokine/chemokine levels) and adaptive, Ag-specific (as judged by MHC tetramer positive T lymphocytes,
IFN-γ secretion and cytotoxicity) immune responses. Finally, in efficacy studies, it is shown that liposomal encapsulation
enhances the ability of CpG ODN to adjuvanate adaptive immune responses against co-administered TAAs after s.c. immunization,
inducing effective anti-tumor activity against both model and syngeneic tumor Ags in murine tumor models of thymoma and melanoma. |
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Keywords: | CpG Liposome Nanoparticle Immunostimulatory Anti-tumor Vaccine |
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