Clinical trials of Cry j 1 and Cry j 2 T-cell epitope peptide-expressing rice in patients with Japanese cedar pollinosis

Shoji Hashimoto,¹ Masatoshi Kawata,¹ Nobusuke Mino,² Satoshi Ogino,³ Noriaki Takeda,⁴ Kayoko Kawashima,⁵ Hidenori Takagi,⁶ Yuhya Wakasa,⁶ Makoto Takano,⁶ Masaki Tanaka,⁷ Yuji Tohda,⁸ Toshio Tanaka⁹

¹ Department of Clinical Laboratory, Osaka Prefectural Hospital Organization Osaka Habikino Medical Center, Osaka, Japan
² Secretariat, Osaka Prefectural Hospital Organization Osaka Habikino Medical Center, Osaka, Japan
³ Osaka Health Care and Allergy Support Organization, Osaka, Japan
⁴ Department of Otolaryngology, University of Tokushima School of Medicine, Tokushima, Japan
⁵ Department of Otorhinolaryngology, Osaka Prefectural Hospital Organization Osaka Habikino Medical Center, Osaka, Japan
⁶ Institute of Agrobiological Sciences, National Agriculture and Food Research Organization, Ibaraki, Japan
⁷ Masaki Clinic, Osaka, Japan
⁸ Department of Respiratory Medicine and Allergology, Kinki University, Osaka, Japan

Abstract

Background: In allergic models, administration of rice that expresses a hybrid peptide consisting of 7 major T cell epitopes of Cry j 1 and Cry j 2 (7Crp), suppressed allergic symptoms, IgE elevation and specific T cell response to Japanese cedar pollen.
Objectives: To evaluate the efficacy and safety of 7Crp-expressing rice in patients with Japanese cedar pollinosis.
Methods: A 24-week randomized, double-blind, placebo-controlled study was performed to see the efficacy of 7Crp on allergic symptoms using scoring systems, in which 45 patients were assigned to take either 5 g, 20 g test rice, or placebo daily. A 96-week open study was also conducted to determine its inhibitory effect on serum IgE and T cell proliferative response for Japanese cedar pollen, in which 10 patients consumed 5 g test rice daily.
Results: No adverse events associated with the test rice occurred, and the intake rate was more than 96%. The test rice did not show suppression of symptoms related to Japanese cedar pollinosis within 24 weeks. However, intake of 5 g test rice led to a significant decrease in T cell response to Japanese cedar pollen during and after the second disperse season in a 96-week open trial, whereas the specific IgE titer remained unchanged.
Conclusion: Tolerability and safety of 7Crp-expressing rice was accepted. Daily intake of up to 20 g transgenic rice did not provide beneficial effects on Japanese cedar pollinosis within 24 weeks, however, continuous intake of 5 g rice might reduce allergen specific T cell response.
Key words: Cry j 1 and Cry j 2, genetically modified rice, Japanese cedar pollinosis, oral allergen immunotherapy, T cell epitope peptide,