Abstract 4673: Selective delivery of tumor specific antigen to dendritic cells by mannose-labeled PLGA nanoparticles to induce immune response for cancer immunotherapy

Abstract

Abstract Objective: To overcome limitation of ex vivo manipulation against dendritic cells (DC) vaccines, we developed mannose-labeled poly(d,l-lactide-co-glycolide) nanoparticles (MN-PLGA-NPs). The MN-PLGA-NPs enabled selective delivery of tumor-specific antigen to mannose receptor overexpressed DCs without ex vivo manipulation. Methods: Conjugation of mannose (MN) and polyvinyl alcohol (PVA) was analyzed by H-NMR. Size and zeta potential of the MN-PLGA-NPs were examined by dynamic light scattering using an electrophoretic light scattering photometer. Selective delivery efficiency of MN-PLGA-NPs to DCs was examined by confocal microscope and flow cytometry. Migration of DCs containing MN-PLGA-NPs was assessed flow cytometry. Therapeutic efficacy of MN-PLGA(OVA+poly I:C)-NPs was examined in EG7 tumor-bearing mouse models. Biological effect and activated CD8+ T cells in tumor tissue were confirmed by immunohistochemistry assay. Results: Conjugation of MN and PVA was confirmed that the peaks for the CH2 of methylene group in PVA was observed at 1.48 ppm and 1.59 ppm, and CH of tetrahydropyran group in MN was observed at 3.40 ppm, 3.49 ppm, 3.76 ppm, and 5.41 ppm. Size and zeta potential of MN-PLGA-NPs were 200 nm formed spherical shape and -10 mV, respectively. Loading efficiency of OVA or poly I:C into MN-PLGA-NPs was 90 % or 45 %, individually. Intracellular uptake of MN-PLGA-NPs in DCs was increased through selective binding between MN and MN-receptor compared to PLGA-NPs. Additionally, DCs containing MN-PLGA-NPs exhibited efficient migration to popliteal lymph node. Therapeutic efficacy of MN-PLGA-NPs showed significant inhibition of tumor growth in EG7 tumor-bearing mice compared to the control (p < 0.001) and PLGA-NPs (p < 0.05), and showed 100% of survival up to 60 days. Additionally, MN-PLGA-NPs treatment group showed a greater number of activated CD8+ T cells in tumor tissue compared to the other groups (p < 0.001), and prevention effect of tumor growth resulted in effectively suppressed compared to the control (p < 0.001) or PLGA-NPs (p < 0.001). Conclusion: MN-PLGA-NPs is an attractive system that can directly activate DC in vivo without ex vivo manipulation, which overcome the limitation of existing DC vaccine. Keyword: dendritic cells, selective delivery, PLGA nanoparticle, cancer immunotherapy. Citation Format: Yeongseon Byeon, Ji Eun Won, Ga Hee Kim, Min Gi Kim, Yeong Min Park, Hee Dong HAN. Selective delivery of tumor specific antigen to dendritic cells by mannose-labeled PLGA nanoparticles to induce immune response for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4673.