自身免疫性疾病的耐受性树突状细胞治疗中的挑战:给药途径。
Challenges in tolerogenic dendritic cell therapy for autoimmune diseases: the route of administration.
发表日期:2023
作者:
María José Mansilla, Catharien M U Hilkens, Eva M Martínez-Cáceres
来源:
ARTHRITIS RESEARCH & THERAPY
摘要:
在自身免疫性疾病治疗中,耐受性树突状细胞(tolDCs)是一种具有潜力的治疗策略,因为它们能够以特异性抗原重塑和调节病理免疫反应,与传统的免疫抑制治疗相比,其对免疫系统的不良影响较小。tolDC疗法已在多发性硬化症(MS)、1型糖尿病(T1D)和类风湿性关节炎(RA)等多个自身免疫性疾病的实验模型中证明了安全性和疗效。此外,来自I期临床试验的数据表明tolDC治疗对于MS、T1D和RA患者是安全和耐受的。然而,需要优化各种参数以增加tolDC的疗效。在这方面,一个重要参数是确定最适宜的给药途径。在实验模型和I期临床试验中已经使用了多种给药途径,如静脉注射、皮下注射、腹腔内注射、皮内注射、淋巴结内注射和关节内注射。本综述总结了在MS、T1D、RA及其动物模型中,在tolDC疗法的临床和前期研究以及成熟肽段负载DC用于癌症免疫疗法和体内细胞跟踪实验中获得的数据,并旨在确定与最可行、最安全和最有效的治疗用途相关的tolDC给药途径。
© 作者2023年出版者牛津大学出版社代表英国免疫学学会的《xxxx》杂志
Tolerogenic dendritic cells (tolDCs) are a promising strategy to treat autoimmune diseases since they have the potential to re-educate and modulate pathological immune responses in an antigen-specific manner and, therefore, have minimal adverse effects on the immune system compared to conventional immunosuppressive treatments. TolDC therapy has demonstrated safety and efficacy in different experimental models of autoimmune disease, such as multiple sclerosis (MS), type 1 diabetes (T1D), and rheumatoid arthritis (RA). Moreover, data from phase I clinical trials have shown that therapy with tolDCs is safe and well tolerated by MS, T1D, and RA patients. Nevertheless, various parameters need to be optimized to increase tolDC efficacy. In this regard, one important parameter to be determined is the most appropriate route of administration. Several delivery routes, such as intravenous, subcutaneous, intraperitoneal, intradermal, intranodal, and intraarticular routes, have been used in experimental models as well as in phase I clinical trials. This review summarizes data obtained from preclinical and clinical studies of tolDC therapy in the treatment of MS, T1D, and RA and their animal models, as well as data from the context of cancer immunotherapy using mature peptide-loaded DC, and data from in vivo cell tracking experiments, to define the most appropriate route of tolDC administration in relation to the most feasible, safest, and effective therapeutic use.© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology.