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丘比特与普赛克系统:用于晚期癌症的诊断与治疗。

Cupid and Psyche system for the diagnosis and treatment of advanced cancer.

机构信息

Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo.

Isotope Science Center, The University of Tokyo.

出版信息

Proc Jpn Acad Ser B Phys Biol Sci. 2019;95(10):602-611. doi: 10.2183/pjab.95.041.

Abstract

In advanced cancer patients, malignant cells invade and disseminate within normal cells and develop resistance to therapy with additional genetic mutations, which makes radical cure very difficult. Precision medicine against advanced cancer is hampered by the lack of systems aimed at multiple target molecules within multiple loci. Here, we report the development of a versatile diagnostic and therapeutic system for advanced cancer, named the Cupid and Psyche system. Based on the strong non-covalent interaction of streptavidin and biotin, a low immunogenic mutated streptavidin, Cupid, and a modified artificial biotin, Psyche, have been designed. Cupid can be fused with various single-chain variable fragment antibodies and forms tetramer to recognize cancer cells precisely. Psyche can be conjugated to a wide range of diagnostic and therapeutic agents against malignant cells. The Cupid and Psyche system can be used in pre-targeting therapy as well as photo-immunotherapy effectively in animal models supporting the concept of a system for precision medicine for multiple targets within multiple loci.

摘要

在晚期癌症患者中,恶性细胞会在正常细胞内侵袭和扩散,并产生额外的基因突变,从而对治疗产生抗药性,这使得根治变得非常困难。针对晚期癌症的精准医学受到缺乏针对多个靶点的多个目标分子的系统的限制。在这里,我们报告了一种名为丘比特与普赛克系统的多功能诊断和治疗晚期癌症的系统的开发。基于链霉亲和素和生物素的强非共价相互作用,设计了一种低免疫原性的突变链霉亲和素丘比特和一种改良的人工生物素普赛克。丘比特可以与各种单链可变片段抗体融合,并形成四聚体以精确识别癌细胞。普赛克可以与针对恶性细胞的广泛的诊断和治疗剂结合。丘比特与普赛克系统可有效地用于预靶向治疗以及光免疫治疗,为多靶点多部位精准医学系统的概念提供了支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cf5/6920082/a9232cda7c00/pjab-95-602-g001.jpg

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