Original ArticleTherapeutic efficacy of cancer vaccine adjuvanted with nanoemulsion loaded with TLR7/8 agonist in lung cancer model
Graphical Abstract
Schematic illustration of the cancer immunotherapy based on cancer vaccines adjuvanted with nanoemulsion (NE) loaded with a TLR7/8 agonist (R848) (NE [R848]) in subcutaneous and orthotopic mouse lung cancer models. NE (R848) stimulates dendritic cells (DCs), proliferates T cells, and converts pro-tumoral immune cells into antitumoral ones, resulting in synergistic antitumor immune responses with immune checkpoint inhibitors (anti-programmed-death-1 [anti-PD-1]).
Section snippets
Cell culture and animals
The ASB-XIV murine lung carcinoma cell line was purchased from Cell Lines Service (CLS, Eppelheim, Germany). ASB-XIV cells were maintained in Dulbecco's modified Eagle's medium with 10% fetal bovine serum (Gibco, Waltham, MA, USA), 100 U/mL penicillin, and 100 μg/mL streptomycin (Gibco) at 37 °C with 5% CO2. BALB/c mice (7 weeks old, female) were purchased from Orient Bio, Inc. (Seongnam, Republic of Korea). All procedures were performed in accordance with the Guide for the Care and Use of
Multifunctional immunomodulatory effects of NE (R848) in vitro: T cell activations and polarization of immunosuppressive cells into immunostimulatory APCs
The multifunctional immunomodulatory effect of NE (R848)-based cancer vaccines stimulates immune responses and ameliorates immune suppression of the TME. NE denotes a squalene-based oil-in-water emulsion comprising 5% Span 85 and 5% Tween 80 surfactants to stabilize its structure. Briefly, NE (R848) was synthesized by dispersing R848 in squalene NE using oleic acid (CH3(CH2)7CH=CH(CH2)7COOH), a fatty acid classified as monounsaturated omega 9 and a weak acid.28 As R848 is a weak base because of
Discussion
In this study, we demonstrated both local and systemic antitumor effects of the NE (R848)-adjuvanted cancer vaccine alone and in combination with anti-PD-1 in subcutaneous and orthotopic mouse lung cancer models. Furthermore, we revealed the underlying mechanisms of antitumor activity of a cancer vaccine adjuvanted with NE (R848), which reprograms the TME by converting MDSCs into mature myeloid cells and M2 macrophages into M1 macrophages. These findings were confirmed by the finding that the
CRediT Author Statement
Conceptualization and research design: YTL, M-JA, JK, SK, and S-YK; Conducting experiments: JK, SK, SNL, S-YK, J-EK, KYL, MSK, YMP, and JYH; Data acquisition: JK, SK, SNL, and KL; Data analysis: JK, SK, SNL, KYL, and BMK; Writing the manuscript: JK and SK; Providing expertise and feedback: J-MS, S-HL, JSA, KP, SY, and S-JH; Supervision and final manuscript confirmation: YTL and M-JA. All authors read and approved the final manuscript.
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2022, Medicine in Drug DiscoveryCitation Excerpt :Such poorly immunogenic tumors become the target of tumor vaccine therapy with TLRa. Koh et al. developed a nanoemulsion loaded with TLR7/8a R848 combined with anti-PD-1 antibody to demonstrate synergistic effect in inhibiting orthotopic lung cancer in mice [110]. Also, TLR7/8a imiquimod combined with pembrolizumab was approved by FDA for stage IIIB-IV melanoma treatment (NCT03276832) [111].
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2021, Colloids and Interface Science CommunicationsCitation Excerpt :The enhanced bio-interactions of NEs with targeted cells improves drug absorption and bioavailability [155]. Inhalable NEs have been formulated toward active targeting to treat respiratory disorders such as lung cancer and asthma [156,157]. Aerosolized NEs have been formulated as vaccines against respiratory pathogens and proven to evoke robust immune responses [158].
Funding
This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIT) (Grant Nos. 2017R1A5A1014560, 2018M3A9H4078701, 2020R1A2C3006888, 2017M3C9A6044633, and 2017H1A2A1044327).
Conflicts of interests
None declared.
- 1
These authors equally contributed to this work.