Diminished viability of human ovarian cancer cells by antigen-specific delivery of carbon monoxide with a family of photoactivatable antibody-photoCORM conjugates,Chemical Science

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Diminished viability of human ovarian cancer cells by antigen-specific delivery of carbon monoxide with a family of photoactivatable antibody-photoCORM conjugates
Chemical Science ( IF 7.6 ) Pub Date : 2019-11-20 , DOI: 10.1039/c9sc03166a
Brian Kawahara ₁ , Lucy Gao ₂ , Whitaker Cohn ₂ , Julian P Whitelegge ₂ , Suvajit Sen ₃ , Carla Janzen ₃ , Pradip K Mascharak ₁

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Carbon monoxide (CO)-releasing antibody conjugates were synthesized utilizing a photoactivatable CO-releasing molecule (photoCORM) and mouse monoclonal antibodies linked by a biotin-streptavidin system. Different monoclonal antibodies raised against different surface-expressed antigens that are implicated in ovarian cancer afforded a family of antibody-photoCORM conjugates (Ab-photoCORMs). In an immunosorbent/cell viability assay, Ab-photoCORMs accumulated onto ovarian cancer cells expressing the target antigens, delivering cytotoxic doses of CO in vitro. The results described here provide the first example of an “immunoCORM”, a proof-of-the-concept antibody-drug conjugate that delivers a gaseous molecule as a warhead to ovarian cancer.

中文翻译：

通过一氧化碳与一系列光活化抗体-photoCORM 偶联物的抗原特异性递送降低人卵巢癌细胞的活力

利用可光活化的 CO 释放分子 (photoCORM) 和通过生物素-链霉亲和素系统连接的小鼠单克隆抗体合成释放一氧化碳 (CO) 的抗体偶联物。针对与卵巢癌有关的不同表面表达抗原产生的不同单克隆抗体提供了一个抗体-photoCORM 偶联物 (Ab-photoCORM) 家族。在免疫吸附剂/细胞活力测定中，Ab-photoCORMs 积累到表达靶抗原的卵巢癌细胞上，在体外提供细胞毒性剂量的 CO 。此处描述的结果提供了“immunoCORM”的第一个示例，这是一种概念验证的抗体-药物偶联物，可将气体分子作为弹头输送到卵巢癌。

更新日期：2019-11-20

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