Pore size-dependent immunogenic activity of mesoporous silica-based adjuvants in cancer immunotherapy

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.