Transgenic rice-based peptide immunotherapy for Japanese cedar pollinosis: From T-cell epitope discovery to clinical...

Japanese cedar (JC) pollinosis affects more than 30 million people in Japan and represents a major public health burden. Although allergen immunotherapy is the only disease-modifying treatment, its clinical application is limited by the requirements of prolonged treatment and the risk of IgE-mediated adverse reactions, including anaphylaxis. Peptide immunotherapy using short T-cell epitopes has emerged as a promising strategy to induce antigen-specific immune tolerance while minimizing these risks. In Japan, seven dominant human T-cell epitopes were identified from the major JC pollen allergens Cry j 1 and Cry j 2, leading to the development of transgenic rice expressing a hybrid peptide (7Crp) as an edible oral vaccine. The protein body I (PB-I) containing 7Crp in transgenic rice functions as a natural oral drug delivery system (DDS), protecting 7Crp from gastrointestinal degradation and facilitating its delivery to the gut-associated lymphoid tissue, where immune tolerance is induced. In small-scale clinical studies, oral administration of the transgenic rice seeds suppressed T-cell proliferative responses, modulated cytokine production, and improved medication score and allergy-related quality of life without treatment-related allergic adverse events. Furthermore, our recent retrospective follow-up study suggests that the improvements in allergy-related quality of life may persist after cessation of treatment, supporting the hypothesis that repeated oral administration of 7Crp-rice has disease-modifying potential. This review summarizes the development of transgenic rice-based peptide immunotherapy for JC pollinosis, from T-cell epitope discovery to preclinical and clinical studies, and discusses its future clinical translation as a safe, scalable, and potentially curative antigen-specific immunotherapy.