4.6 Article

Therapeutic efficacy of cancer vaccine adjuvanted with nanoemulsion loaded with TLR7/8 agonist in lung cancer model

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ELSEVIER
DOI: 10.1016/j.nano.2021.102415

Keywords

Immunotherapy; Adjuvant; Toll-like receptor agonist; Immunosuppression; Immune checkpoint inhibitorAbbreviations; APC; antigen-presenting cell; DC; dendritic cell; IFN; interferon; IL; interleukin; iNOS; inducible nitric oxide synthase; MDSC; myeloid-derived suppressor cell; NE; nanoemulsion; NE (R848); nanoemulsion loaded with a TLR7; 8 agonist (R848); NK; natural killer; PD-1; programmed death-1; PD-L1; PD-ligand 1; TAM; tumor-associated macrophage; TEM; transmission electron microscopy; TGF; transforming growth factor; TL; tumor lysate; TLR; Toll-like receptor; TME; tumor microenvironment; TNF; tumor necrosis factor

Funding

  1. National Research Foundation of Korea (NRF) - Korean government (MSIT) [2017R1A5A1014560, 2018M3A9H4078701, 2020R1A2C3006888, 2017M3C9A6044633, 2017H1A2A1044327]
  2. National Research Foundation of Korea [2020R1A2C3006888, 2017H1A2A1044327, 2018M3A9H4078701, 2017M3C9A6044633] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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A cancer vaccine adjuvanted with nanoemulsion (NE) loaded with TLR7/8 agonist (R848) demonstrated robust antitumor immune responses in both subcutaneous and orthotopic mouse lung cancer models, potentially prolonging survival by activating antitumor immunity and reprogramming immunosuppression.
Although immune checkpoint inhibitors have significantly improved clinical outcomes in various malignant cancers, only a small proportion of patients reap benefits, likely due to the low number of T cells and high number of immunosuppressive cells in the tumor microenvironment (TME) of patients with advanced disease. We developed a cancer vaccine adjuvanted with nanoemulsion (NE) loaded with TLR7/8 agonist (R848) and analyzed its therapeutic effect alone or in combination with immune checkpoint inhibitors, on antitumor immune responses and the reprogramming of suppressive immune cells in the TME. NE (R848) demonstrated robust local and systemic antitumor immune responses in both subcutaneous and orthotopic mouse lung cancer models, inducing tumor-specific T cell activation and mitigating T cell exhaustion. Combination with anti-PD-1 antibodies showed synergistic effects with respect to therapeutic efficacy and survival rate. Thus, NE (R848)-based cancer vaccines could prevent tumor recurrence and prolong survival by activating antitumor immunity and reprogramming immunosuppression. (c) 2021 Elsevier Inc. All rights reserved.

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