文章：

人类肿瘤的放射免疫治疗

Radioimmunotherapy of human tumours

原文发布日期：2015-05-22

DOI: 10.1038/nrc3925

类型: Review Article

开放获取: 否

要点：

1. Antibodies with practical healthcare applications are being introduced into modern medicine at a rapid pace by academic laboratories and industry. Therapeutic applications of these biologics are becoming increasingly important for cancer, either by promoting the body's own defence against the tumour or as a carrier for immunotoxins, drugs or radiation.
2. Radioimmunotherapy, which is the subject of this Review, exploits the immune protein as a carrier for radioactive isotopes, tracers or targeted therapeutics. The radioantibody is introduced into the blood or a body cavity such as the peritoneum, pleura or intrathecal space, and is carried to its natural target or antigen-binding site on the tumour cell by blood flow, diffusion or the bulk flow of fluid.
3. Cancer cells naturally produce cancer-associated biological molecules, which are adaptive features of malignant change that are suitable as antigenic binding sites owing to their relatively high abundance in cancer cells in comparison to normal tissues. These cancer-associated antigens may be located in the membrane, cytoplasm or organelles, including the nucleus. Typical concentrations of target antigens are in the nanomolar to low micromolar range.
4. Cancer-selective antibodies and related immunoproteins are particularly well suited for conjugation with radioisotopes, for the purpose of detection or targeted radiotherapy. As a rule of thumb, the concentration of antibody at the binding site should approximate but not exceed the concentration of antigen (that is, the nanomolar range), and this amount of carrier is enormous relative to the required concentrations of attached radioisotopes for detection or therapy. This is because radioisotopes are among the most energetic moieties known, and this energy can be used for imaging or radiotherapy when attached to antibodies, in the femto-molar to pico-molar range.

要点翻译：

1. 具有实际医疗应用价值的抗体正通过学术实验室和工业界快速引入现代医学。这些生物制剂在癌症治疗中的应用日益重要，无论是通过激活人体自身防御机制对抗肿瘤，还是作为免疫毒素、药物或辐射的载体。
2. 本文述评的主题——放射免疫疗法，正是利用免疫蛋白作为放射性同位素、示踪剂或靶向治疗药物的载体。放射性抗体通过血液流动、扩散或体液整体流动，被引入血液或腹膜、胸膜、鞘内等体腔，并抵达其在肿瘤细胞上的天然靶点或抗原结合位点。
3. 癌细胞会自然产生癌症相关生物分子，这些分子是恶性转化的适应性特征，由于其在癌细胞中的丰度显著高于正常组织，因而适合作为抗原结合位点。这些癌症相关抗原可能位于细胞膜、细胞质、细胞器（包括细胞核）中。靶抗原的典型浓度范围在纳摩尔至低微摩尔之间。
4. 癌症选择性抗体及相关免疫蛋白特别适合与放射性同位素偶联，用于检测或靶向放射治疗。根据经验法则，结合位点的抗体浓度应接近但不超出抗原浓度（即纳摩尔范围），且相对于检测或治疗所需的放射性同位素浓度，此类载体的用量极为庞大。这是因为放射性同位素是目前已知能量最高的分子组分，当与抗体结合时，即使在飞摩尔至皮摩尔浓度范围内，其释放的能量仍可用于成像或放射治疗。

英文摘要：

The eradication of cancer remains a vexing problem despite recent advances in our understanding of the molecular basis of neoplasia. One therapeutic approach that has demonstrated potential involves the selective targeting of radionuclides to cancer-associated cell surface antigens using monoclonal antibodies. Such radioimmunotherapy (RIT) permits the delivery of a high dose of therapeutic radiation to cancer cells, while minimizing the exposure of normal cells. Although this approach has been investigated for several decades, the cumulative advances in cancer biology, antibody engineering and radiochemistry in the past decade have markedly enhanced the ability of RIT to produce durable remissions of multiple cancer types.

摘要翻译： 

尽管近年来我们对肿瘤发生分子机制的理解取得了进展，但癌症的根治仍是一个棘手难题。一种颇具前景的治疗策略是利用单克隆抗体，将放射性核素选择性递送至癌细胞表面相关抗原。这种放射免疫治疗（RIT）可在最大限度减少正常细胞暴露的同时，向癌细胞输送高剂量治疗性辐射。尽管该方法已研究数十年，但过去十年在癌症生物学、抗体工程及放射化学领域的累积进展，已显著提升RIT诱导多种癌症持久缓解的能力。

原文链接：

Radioimmunotherapy of human tumours