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Int J Biol Macromol.に論文が掲載されました。（細胞膜透過型アルブミンの舌下免疫療法への応用）

2022/10/05

Cell-penetrating albumin enhances the sublingual delivery of antigens through macropinocytosis.

Maeda H, Ichimizu S, Watanabe H, Hamasaki K, Chikamatsu M, Murata R, Yumoto N, Seki T, Katsuki H, Otagiri M, Maruyama T.

Int J Biol Macromol. 2022 Sep 17;221:1439-1452. doi: 10.1016/j.ijbiomac.2022.09.132.

Abstract: Innovations in oral immunotherapy have greatly advanced the therapeutic control of allergies. However, these therapeutic effects suffer from the fact that the amount of antigen delivered to antigen-presenting cells is limited given the formulations that are currently available. We recently designed a cell-penetrating albumin and found that this modified albumin enters cells via the induction of macropinocytosis. Herein, we report on a novel system for delivering antigens based on cell-penetrating albumin-inducible macropinocytosis that allows larger amounts of antigens to be delivered to antigen-presenting cells. A treatment with cell-penetrating albumin significantly increased the permeability of ovalbumin (45 kDa) or dextran (2000 kDa) on monolayers derived from human oral squamous carcinoma cells. Flow cytometric analyses showed that the cell-penetrating albumin treatment resulted in a significant elevation in the amount of dextran that was delivered to two types of antigen-presenting cells. Finally, mice that had been sensitized by Japanese cedar pollen extract (JCPE) and cell-penetrating albumin showed a decline in the frequency of nose-rubbing against a subsequent intranasal administration of JCPE. These findings suggest that the sublingual administration of cell-penetrating albumin efficiently delivers antigens to antigen-presenting cells via the induction of macropinocytosis, resulting in an enhancement in the therapeutic effect of sublingual immunotherapy.

Keywords: Cell-penetrating peptide; Human serum albumin; Sublingual immunotherapy.