title: Pore size-dependent immunogenic activity of mesoporous silica-based adjuvants in cancer immunotherapy.
abstract: Commonly used aluminum hydroxide (Alum) adjuvant provokes a strong type 2 helper T cell (Th2) response for mediating antibody production but is rather ineffective for disease prevention that requires type 1 helper T cell (Th1) response for mediating cellular immunity in human vaccination. Here, for the purpose of inducing Th1 antitumor immunity, a mesoporous silica (MS)-based adjuvant is prepared. Three kinds of MS particles with nearly identical particle size and surface area but different pore sizes of 4, 7 and 10 nm were prepared. No serious in vitro cytotoxicity was observed for the MS particles at 5, 20, 50, and 100 μg/mL. Pathogen-associated molecular patterns (PAMPs) were immobilized with apatite (Ap) on MS to prepare the MS-based and PAMP-loaded adjuvants (MS-Ap-PAMP adjuvants). Macrophage-like cells cultured in the presence of MS-Ap-PAMP adjuvant with a MS pore size of 10 nm showed the maximum in vitro immunogenic activity. Injection of the MS-Ap-PAMP adjuvant with a MS pore size of 10 nm in combination with liquid nitrogen-treated tumor tissue (derived from Lewis lung carcinoma cells) to C57BL/6 mice markedly inhibited the development of rechallenged tumor in vivo, while no such antitumor immunity was induced in injection of Alum mixed with PAMP in combination with liquid nitrogen-treated tumor tissue. The MS-Ap-PAMP adjuvant contributed to the elicitation of a potent systemic Th1 antitumor immunity in vivo.
authors: Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, 305-8566, Japan.
authors: Xiupeng
authors: X
authors: Wang
authors: Xia
authors: X
authors: Li
authors: Atsuo
authors: A
authors: Ito
authors: Yu
authors: Y
authors: Sogo
authors: Tadao
authors: T
authors: Ohno
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000327:Adsorption; D000818:Animals; D001031:Apatites / Q000737:chemistry; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D009584:Nitrogen; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000276:Adjuvants, Immunologic; D001031:Apatites; D012822:Silicon Dioxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009584:Nitrogen
keywords: adjuvant; immune; mesoporous silica; pore size