R&D Immunology, Sigma-Tau SpA, Pomezia, Rome, Italy.
Cancer Biother Radiopharm. 2010 Oct;25(5):563-70. doi: 10.1089/cbr.2010.0797. Epub 2010 Sep 23.
Hen egg white avidin is increasingly used in the clinic as part of multifactor treatments such as pretargeted radionuclide therapy of cancer or as an antidote of biotinylated drugs. Taking into account that naturally occurring human antiavidin antibodies (HAVA) are common in humans, the present work investigates avidin immunogenicity as part of risk/benefit evaluations. Sera from 139 oncology patients naive to avidin were confirmed to exhibit HAVA with lognormally distributed titers. HAVA were boosted after avidin treatment, with no correlation with the avidin dose or with the basal titer. No antibody-related clinical symptoms were observed in 21 HAVA-positive patients treated with avidin. In mouse models, high mouse antiavidin antibody titers, induced to simulate the worst human condition, neither reduced the biotin uptake of intratissue-injected avidin nor affected the capacity of intravenously injected avidin to clear a biotinylated drug from circulation. In both models the avidin treatment was well tolerated. Results indicate that avidin immunogenicity does not affect its safety and efficacy, thus encouraging its further use in clinical applications.
鸡蛋白亲和素作为多因素治疗的一部分，如癌症的预靶向放射性核素治疗或作为生物素化药物的解毒剂，在临床上的应用越来越广泛。考虑到天然存在的人类抗亲和素抗体（HAVA）在人类中很常见，本研究将亲和素免疫原性作为风险/收益评估的一部分进行了研究。139 名对亲和素有治疗经验的肿瘤患者的血清被证实具有正态分布滴度的 HAVA。亲和素治疗后 HAVA 被增强，与亲和素剂量或基础滴度无关。在 21 名接受亲和素治疗的 HAVA 阳性患者中，未观察到与抗体相关的临床症状。在模拟最坏人类情况的小鼠模型中，诱导产生的高小鼠抗亲和素抗体滴度既没有降低组织内注射的亲和素的生物素摄取，也没有影响静脉注射的亲和素从循环中清除生物素化药物的能力。在这两种模型中，亲和素治疗都耐受良好。结果表明，亲和素免疫原性不影响其安全性和疗效，从而鼓励其在临床应用中进一步使用。
