Toll-like receptor 3-induced immune response by poly(d,l-lactide-co-glycolide) nanoparticles for dendritic cell-based cancer immunotherapy

Abstract

Dendritic cells (DCs) are potent professional antigen-presenting cells that are capable of initiating a primary immune response and activating T cells, and they play a pivotal role in the immune responses of the host to cancer. Prior to antigen presentation, efficient antigen and adjuvant uptake by DCs is necessary to induce their maturation and cytokine generation. Nanoparticles (NPs) are capable of intracellular delivery of both antigen and adjuvant to DCs. Here, we developed an advanced poly(d,l-lactide-co-glycolide) (PLGA)-NP encapsulating both ovalbumin (OVA) as a model antigen and polyinosinic-polycytidylic acid sodium salt (Toll-like receptor 3 ligand) as an adjuvant to increase intracellular delivery and promote DC maturation. The PLGA-NPs were taken up by DCs, and their uptake greatly facilitated major histocompatibility class I antigen presentation in vitro. Moreover, vaccination with PLGA-NP-treated DCs led to the generation of ovalbumin-specific CD8⁺ T cells, and the resulting antitumor efficacy was significantly increased in EG.7 and TC-1 tumor-bearing mice compared to control mice (P<0.01). Taken together, these findings demonstrated that the PLGA-NP platform may be an effective method for delivering tumor-specific antigens or adjuvants to DCs.

Keywords:

• cancer immunotherapy
• PLGA nanoparticles
• antigen delivery

Supplementary materials

Figure S1 Release behavior of OVA from PLGA (OVA + poly I:C)-NP.

Note: The data are represented as mean ± SD (n=3).

Abbreviations: NPs, nanoparticles; OVA, ovalbumin; PLGA, poly(d,l-lactide-co-glycolide); poly I:C, polyinosinic-polycytidylic acid; SD, standard deviation.

Figure S2 Intracellular delivery of PLGA (OVA + poly I:C)-NP in DCs. OVA was labeled with TRICT fluorescence and poly I:C labeled with FITC. Scale bar: 20 μm.

Abbreviations: DCs, dendritic cells; FITC, fluorescein isothiocyanate; NPs, nanoparticles; OVA, ovalbumin; PLGA, poly(d,l-lactide-co-glycolide); poly I:C, polyinosinic-polycytidylic acid; TRITC, Tetramethylrhodamine.

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (NRF-2015R1A2A1A13001713, NRF-2016R1A5A2012284, NRF-2015R1A2A2A04003620) (Y-MP and YJL). This work was supported by Basic Research Laboratory Program through the NRF funded by the Ministry of Science (NRF-2016R1A2B2007327), and ICT and Future Planning (No 2013R1A4A1069575) (HDH). This study was supported by a grant from the National R&D program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea (1520100) (J-WL, and HDH). The authors would like to express their thanks to Ga Hee Kim, Min Gi Kim, and Hyung Jun Ahn for data analysis.

Disclosure

The authors report no conflicts of interest in this work.