抗体-化疗药物偶联物（Antibody-drug conjugates, ADC）充分发挥了抗体和化疗药物二者的优势，具有高效、毒副作用低等特点，对难治性复发性肿瘤具有显著疗效，是下一代抗肿瘤抗体药物研究领域最新的发展方向。小细胞肺癌（Small-cell lung cancer, SCLC）恶性程度高，目前尚无有效的治疗方法。CD56分子在小细胞肺癌中高表达且表达率约为100%，是靶向小细胞肺癌ADC药物研发理想的靶点。α-Amanitin是强烈的RNA聚合酶II抑制剂，对肿瘤细胞具有一定的选择杀伤能力。前期工作中，申请者筛选到1株IgG1型高亲合力抗CD56的抗体，建立了多种抗体-化疗药物的偶联方法。在此基础上，本课题拟将抗CD56抗体与α-Amanitin偶联，构建一种新型的ADC靶向化疗药物，以期能体内靶向小细胞肺癌组织，在高效杀伤肿瘤细胞的同时降低药物对人体的毒副作用。

Antibody-drug conjugates (ADCs) show the advantages of both antibody and chemotherapeutics. Because of their high efficiency, low toxicity and evident curative effect to refractory recurring cancers, ADCs are promising as the next generation of antibody antitumor drugs. Now, there is no effective treatment for Small-cell Lung Cancer (SCLC) which is with high grade malignancy. In the case of SCLC, the positive rate of CD56 is 100% which makes it a great target for ADCs. Alpha-Amanitin is a strong RNA polymerase inhibitor and can selectively kill tumor cells. Recently, it is used as targeting molecule. In prior research, applicant screened an lgG1 type high-affinity antiCD56 antibody and synthesized more than 20 kinds of linkers with bifunctional conjugate groups. Then, several antibody anticancer drug conjugating methods was established. Based on it, a new type of ADC candidate will be constructed by conjugating antiCD56 antibody and Alpha-Amanitin.