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

• Published in: Nanomedicine 2021-10, Vol.37, p.102415-102415, Article 102415
• Main Authors: Koh, Jiae, Kim, Sohyun, Lee, Sang Nam, Kim, Sun-Young, Kim, Jung-Eun, Lee, Kyoung Young, Kim, Mi Soon, Heo, Jae Yeong, Park, Young Mee, Ku, Bo Mi, Sun, Jong-Mu, Lee, Se-Hoon, Ahn, Jin Seok, Park, Keunchil, Yang, Siyoung, Ha, Sang-Jun, Lim, Yong Taik, Ahn, Myung-Ju
• Format: Article
• Language: English
• Subjects: Adjuvant; Adjuvants, Immunologic - pharmacology; Animals; Cancer Vaccines - chemistry; Cancer Vaccines - immunology; Cancer Vaccines - pharmacology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Disease Models, Animal; Drug Synergism; Emulsions - chemistry; Emulsions - pharmacology; Humans; Imidazoles - pharmacology; Immune checkpoint inhibitor; Immune Checkpoint Inhibitors - pharmacology; Immunosuppression; Immunotherapy; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Lymphocyte Activation - drug effects; Mice; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - immunology; Toll-Like Receptor 7 - agonists; Toll-Like Receptor 7 - genetics; Toll-Like Receptor 8 - agonists; Toll-Like Receptor 8 - genetics; Toll-like receptor agonist; Tumor Microenvironment - drug effects
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2021.102415

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. 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]). [Display omitted]