A novel monoclonal antibody targeting coxsackie virus and adenovirus receptor inhibits tumor growth in vivo.
A novel monoclonal antibody targeting coxsackie virus and adenovirus receptor inhibits tumor growth in vivo.
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DOI：
10.1038/srep40400
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发表时间：
2017-01-11
影响因子：
4.6
通讯作者：
Masuda T
中科院分区：
文献类型：
--
作者：
Kawada M;Inoue H;Kajikawa M;Sugiura M;Sakamoto S;Urano S;Karasawa C;Usami I;Futakuchi M;Masuda T
为了制备新型抗肿瘤抗体，我们利用逆转录病毒介导的表达方法进行了信号序列捕获，并确定科萨基病毒和腺病毒受体（CXADR）为合适的靶点。我们开发了抗人CXADR的单克隆抗体，并发现一种抗体（6G10A）在体内显著抑制人前列腺癌细胞的皮下以及原位异种移植物的生长。此外，6G10A还抑制表达CXADR的其他癌症异种移植物，例如胰腺癌和结肠直肠癌细胞。CXADR的敲低和过表达证实了其抗肿瘤活性对CXADR表达的依赖性。我们对其作用的研究表明，6G10A主要通过抗体依赖性细胞毒性和补体依赖性细胞毒性发挥其抗肿瘤活性。此外，6G10A与人肿瘤组织如前列腺、肺和脑反应，其中每一种都表达CXADR。虽然我们需要进一步评估其在人体组织中的反应性和安全性，但我们的结果表明，新型抗CXADR抗体可能是癌症免疫治疗的可行候选者。
To create a new anti-tumor antibody, we conducted signal sequence trap by retrovirus-meditated expression method and identified coxsackie virus and adenovirus receptor (CXADR) as an appropriate target. We developed monoclonal antibodies against human CXADR and found that one antibody (6G10A) significantly inhibited the growth of subcutaneous as well as orthotopic xenografts of human prostate cancer cells in vivo. Furthermore, 6G10A also inhibited other cancer xenografts expressing CXADR, such as pancreatic and colorectal cancer cells. Knockdown and overexpression of CXADR confirmed the dependence of its anti-tumor activity on CXADR expression. Our studies of its action demonstrated that 6G10A exerted its anti-tumor activity primarily through both antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Moreover, 6G10A reacted with human tumor tissues, such as prostate, lung, and brain, each of which express CXADR. Although we need further evaluation of its reactivity and safety in human tissues, our results show that a novel anti-CXADR antibody may be a feasible candidate for cancer immunotherapy.