1. Academic Validation
  2. A Therapeutic Whole-Tumor-Cell Vaccine Covalently Conjugated with a TLR7 Agonist

A Therapeutic Whole-Tumor-Cell Vaccine Covalently Conjugated with a TLR7 Agonist

  • Cells. 2022 Jun 21;11(13):1986. doi: 10.3390/cells11131986.
Huju Chi 1 Yue Hao 2 Xia Wang 1 Li Tang 3 Yongqiang Deng 4 Xianxiong Chen 4 Feng Gao 4 Ou Sha 1 4 Guangyi Jin 2
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Health Science Center, Shenzhen University, Shenzhen 518000, China.
  • 2 School of Pharmaceutical Sciences, International Cancer Center, Health Science Center, Shenzhen University, Shenzhen 518000, China.
  • 3 College of Health Science and Environmental Engineering, Shenzhen Technology University, Shenzhen 518000, China.
  • 4 School of Dentistry, Health Science Center, Shenzhen University, Shenzhen 518000, China.
Abstract

A single-protein or -peptide vaccine is not sufficient to arouse immune responses in Cancer therapy. A whole-tumor-cell vaccine with complete Cancer cell antigens and all conformations elicits robust immune responses and is a promising method for the treatment of advanced malignant tumors. In this study, we used 5-azacitidine to stimulate B16-F10 melanoma cells to express Toll-like Receptor (TLR) 3 on the cell surface and then chemically linked SZU-106, a small-molecule TLR7 Agonist, to the cell surface with a pegylated linker to produce a novel whole-tumor-cell vaccine, abbreviated as Aza-BFcell-106. The vaccine stimulated mouse splenic lymphocytes and bone marrow-derived dendritic cells to secrete cytokines, promoted the maturation of dendritic cells and enhanced the capability of dendritic cells to present antigens. In a mouse model of melanoma, the vaccine effectively inhibited tumor growth, decreased tumor volume and prolonged survival. Further combination of the vaccine with a chemokine inhibitor, reparixin, significantly increased the infiltration of CD4+ and CD8+ T cells into the tumor environment, while the antitumor effect was significantly enhanced. The whole-tumor-cell vaccine Aza-BFcell-106 induced immune-activating responses in both in vitro and in vivo experiments, indicating that this vaccine has great potential to treat advanced malignant tumors.

Keywords

5-azacytidine; cancer immunotherapy; reparixin; toll-like receptor 7 agonist; whole-tumor-cell vaccine.

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