“铁门”靶向抗体研究进展

Research Progress of “Iron Gate” Targeting Antibody

摘要: 铁元素作为生命体不可或缺的微量营养素，广泛参与生命体的多种生物功能中，如细胞呼吸、DNA复制、细胞周期、活性氧产生。正常情况下，机体铁稳态受到严格调控。转铁蛋白受体1 (transferrin receptor 1, TFR1)这一“铁门”作为细胞摄取铁的主要途径，在维持机体铁稳态中起关键作用。TFR1表达受到严格调控。研究发现，血脑屏障管腔膜上TFR1表达水平远高于外周毛细血管内皮细胞，这种高表达属性已被证明与维持脑内铁稳态有关。血脑屏障的存在阻挡了绝大多数药物的脑内渗透，低生物利用度使得药物药效无法发挥。TFR1作为血脑屏障管腔膜上的天然膜受体可以介导生物大分子转铁蛋白的转胞吞。目前基于TFR1抗体的药物脑内递送研究主要围绕TFR1抗体跨血脑屏障转运的潜力开发和TFR1抗体相关药物的脑部疾病治疗展开。除此之外，多份研究表明，机体铁过载有助于肿瘤的发生、发展和转移。TFR1作为细胞摄取铁的主要途径，广泛参与这一过程。通过靶向肿瘤细胞这一“铁门”，TFR1抗体已被广泛用于血液恶性肿瘤、胰腺癌等多种恶性肿瘤的诊治中。本文旨在对靶向细胞“铁门”的TFR1抗体在以上两方面的最新研究进展予以论述。

Abstract: Iron is an indispensable micronutrient for life, and it is widely involved in many biological functions of life, such as cell respiration, DNA replication, cell cycle, and reactive oxygen species production. Under normal circumstances, the body’s iron homeostasis is strictly regulated. The transferrin receptor 1 (TFR1)—“iron gate”, as the main way for cells to take up iron, plays a key role in maintaining iron homeostasis. Expression of TFR1 is strictly regulated. Studies have found that the expression level of TFR1 on the luminal membrane of the blood-brain barrier (BBB) is much higher than that of peripheral capillary endothelial cells. This high expression attribute has been shown to be related to maintaining iron homeostasis in the brain. The presence of the BBB blocks the brain penetration of most drugs, and low bioavailability prevents the drug's efficacy from being exerted. TFR1, as a natural membrane receptor on the luminal membrane of the BBB, can mediate the transcytosis of the biological macromolecule transferrin. At present, the research of TFR1 antibody-based delivery of drugs into the cerebral mainly focuses on the development of the potential of TFR1 antibody to cross the blood-brain barrier and the treatment of brain diseases with TFR1 antibody related drugs. In addition, several studies have shown that iron overload in the body contributes to the occurrence, development, and metastasis of tumor. TFR1, as the main gate for cells to take up iron, is widely involved in this process. By targeting this “iron gate” of tumor cells, TFR1 antibodies have been widely used in the diagnosis and treatment of a variety of malignant tumors including hematological malignancies, pancreatic cancer and so on. This article aims to discuss the latest research progress of the TFR1 antibody targeting the cell “iron gate” in the above two aspects.