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Adjuvant Activity Enhanced by Cross-Linked CpG-Oligonucleotides in β-Glucan Nanogel and Its Antitumor Effect.
- Source :
-
Bioconjugate chemistry [Bioconjug Chem] 2017 Feb 15; Vol. 28 (2), pp. 565-573. Date of Electronic Publication: 2017 Jan 13. - Publication Year :
- 2017
-
Abstract
- Cancer vaccine has the ability to directly eradicate tumor cells by creating and activating cytotoxic T lymphocytes (CTLs). To achieve efficient CTL activity and to induce Th1 responses, it is essential to administer an appropriate adjuvant as well as an antigen. CpG-ODN is known as a ligand of Toll-like receptor 9 (TLR9) and strongly induces Th1 responses. In our previous study, we developed a CpG-ODN delivery system by use of the formation of complexes between ODN and a β-glucan SPG, denoted as CpG/SPG, and demonstrated that CpG/SPG induces high Th1 responses. In this study, we created a nanogel made from CpG/SPG complexes through DNA-DNA hybridization (cross-linked (CL)-CpG). Immunization with CL-CpG induced much stronger antigen-specific Th1 responses in combination with the antigenic protein ovalbumin (OVA) than that with CpG/SPG. Mice preimmunized with CL-CpG and OVA exhibited a long delay in tumor growth and an improved survival rate after tumor inoculation. These immune inductions can be attributed to the improvement of cellular uptake by the combination of increased size and the cluster effect of the β-glucan recognition site in the nanogel structure. In other words, the particle nature of CL-CpG, instead of the semiflexible rod conformation of CpG/SPG, enhanced the efficacy of a cancer vaccine. The present results indicate that CL-CpG can be used as a potent vaccine adjuvant for the treatment of cancers and infectious diseases.
- Subjects :
- Adjuvants, Immunologic pharmacokinetics
Adjuvants, Immunologic therapeutic use
Animals
Cancer Vaccines pharmacokinetics
Cancer Vaccines therapeutic use
Cross-Linking Reagents chemistry
Cytokines immunology
Immunization methods
Mice
Neoplasms immunology
Oligodeoxyribonucleotides pharmacokinetics
Oligodeoxyribonucleotides therapeutic use
Ovalbumin immunology
RAW 264.7 Cells
Toll-Like Receptor 9 immunology
Adjuvants, Immunologic administration & dosage
Cancer Vaccines administration & dosage
Drug Delivery Systems methods
Gels chemistry
Neoplasms prevention & control
Oligodeoxyribonucleotides administration & dosage
beta-Glucans chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4812
- Volume :
- 28
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Bioconjugate chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 27951636
- Full Text :
- https://doi.org/10.1021/acs.bioconjchem.6b00675