Targeting non-human coronaviruses to human cancer cells using a bispecific single-chain antibody.
Targeting non-human coronaviruses to human cancer cells using a bispecific single-chain antibody.
复制标题
使用双特异性单链抗体将非人类冠状病毒靶向人类癌细胞。
DOI：
10.1038/sj.gt.3302535
复制
发表时间：
2005-09
期刊：
影响因子：
5.1
通讯作者：
Gerritsen WR
中科院分区：
文献类型：
--
作者：
Würdinger T;Verheije MH;Raaben M;Bosch BJ;de Haan CA;van Beusechem VW;Rottier PJ;Gerritsen WR
为了探索使用非人类冠状病毒进行癌症治疗的潜力，我们首先确定了它们杀死人类肿瘤细胞的能力。我们发现，猫传染性腹膜炎病毒（FIPV）和猫源化鼠肝炎病毒（fMHV），通常不能感染人类细胞，可以快速有效地杀死人类癌细胞人工表达猫冠状病毒受体氨肽酶N。从这些细胞建立的3-D多层肿瘤球体也被有效地根除。接下来，我们研究了FIPV和fMHV是否可以通过构建一种双特异性单链抗体来靶向人类癌细胞，该抗体一方面针对猫冠状病毒刺突蛋白-负责受体结合和随后通过病毒细胞膜融合进入细胞-另一方面针对人表皮生长因子受体（EGFR）。靶向抗体介导两种冠状病毒对EGFR表达的人癌细胞的特异性感染。此外，在靶向抗体的存在下，感染的癌细胞形成典型的生产性冠状病毒感染的合胞体。通过其强大的细胞毒性，非人冠状病毒对人癌细胞的选择性靶向为进一步研究这些病毒作为抗癌剂的用途提供了理论基础。
To explore the potential of using non-human coronaviruses for cancer therapy, we first established their ability to kill human tumor cells. We found that the feline infectious peritonitis virus (FIPV) and a felinized murine hepatitis virus (fMHV), both normally incapable of infecting human cells, could rapidly and effectively kill human cancer cells artificially expressing the feline coronavirus receptor aminopeptidase N. Also 3-D multilayer tumor spheroids established from such cells were effectively eradicated. Next, we investigated whether FIPV and fMHV could be targeted to human cancer cells by constructing a bispecific single-chain antibody directed on the one hand against the feline coronavirus spike protein – responsible for receptor binding and subsequent cell entry through virus–cell membrane fusion – and on the other hand against the human epidermal growth factor receptor (EGFR). The targeting antibody mediated specific infection of EGFR-expressing human cancer cells by both coronaviruses. Furthermore, in the presence of the targeting antibody, infected cancer cells formed syncytia typical of productive coronavirus infection. By their potent cytotoxicity, the selective targeting of non-human coronaviruses to human cancer cells provides a rationale for further investigations into the use of these viruses as anticancer agents.
登录
查看更多内容
影响因子：
5.4
作者：
COMPTON, SR;STEPHENSEN, CB;HOLMES, KV
通讯作者：
HOLMES, KV
影响因子：
3.5
作者：
Müller, KM;Arndt, KM;Plückthun, A
通讯作者：
Plückthun, A
影响因子：
5.4
作者：
CORAPI, WV;OLSEN, CW;SCOTT, FW
通讯作者：
SCOTT, FW
影响因子：
11.2
作者：
Anderson, BD;Nakamura, T;Peng, KW
通讯作者：
Peng, KW
影响因子：
2.4
作者：
EVERMANN, JF;BAUMGARTENER, L;MCKEIRNAN, AJ
通讯作者：
MCKEIRNAN, AJ