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Open AccessArticle

High Molecular Weight Chitosan-Complexed RNA Nanoadjuvant for Effective Cancer Immunotherapy

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea
NA Vaccine Institute, Seoul 05854, Korea
Department of Biomedical Engineering, Konkuk University, Seoul 05029, Korea
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2019, 11(12), 680;
Received: 6 November 2019 / Revised: 8 December 2019 / Accepted: 11 December 2019 / Published: 14 December 2019
Nucleic acid-based adjuvants have recently emerged as promising candidates for use in cancer vaccines to induce tumor-suppressing immune cells. In this study, we tested whether complexation of a nucleic acid-based adjuvant with chitosan (CTS) modulates immune adjuvant functions. As a nucleic acid-based adjuvant, we used toll-like receptor 3-recognizing RNA adjuvant (RA). Negatively charged RA formed nanoscale polyplexes with cationic CTS that possessed positive zeta potentials. RA/CTS polyplexes exerted dendritic cell (DC)-maturation effects without causing significant DC toxicity. This DC-maturation effect was CTS molecular weight dependent, with RA/CTS polyplexes with a CTS molecular weight of 340 kDa (RA/CTS 340K) producing the greatest effect. Subcutaneous injection of RA/CTS 340K polyplexes with the model tumor antigen ovalbumin exerted a preventive effect against challenge by ovalbumin-expressing tumor cells. It also provided greater inhibitory effects against a second challenge with the same tumor cells compared with other treatments. These protective effects of subcutaneous RA/CTS polyplex treatment were associated with the highest tumor antigen-specific humoral and cellular immune responses after tumor challenge, and with the greatest infiltration of CD4 helper T cell and CD8 T cell into the tumor tissues. Mice vaccinated with ovalbumin and RA/CTS polyplexes showed complete survival, even after repeated challenge with tumor cells. Our results suggest the potential of RA/CTS polyplexes as effective nanoadjuvants in the design of tumor vaccines and cancer immunotherapy. View Full-Text
Keywords: RNA adjuvant; chitosan; nanoadjuvant; cancer vaccine; immunotherapy RNA adjuvant; chitosan; nanoadjuvant; cancer vaccine; immunotherapy
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MDPI and ACS Style

Choi, J.J.; Le, Q.-V.; Kim, D.; Kim, Y.B.; Shim, G.; Oh, Y.-K. High Molecular Weight Chitosan-Complexed RNA Nanoadjuvant for Effective Cancer Immunotherapy. Pharmaceutics 2019, 11, 680.

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