Human antibody VH domains targeting uPAR as candidate therapeutics for cancers

以 uPAR 为靶点的人类抗体 VH 结构域可作为癌症的候选疗法

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作者:Xiaojie Chu, Wei Li, Margaret G Hines, Ilya Lyakhov, John W Mellors, Dimiter S Dimitrov

Abstract

The high expression of uPAR has been linked to tumor progression, invasion, and metastasis in several types of cancer. Such overexpression of uPAR makes it a potential target for immunotherapies across common cancers such as breast, colorectal, lung, ovarian cancer, and melanoma. In our study, two high-affinity and specific human VH domain antibody candidates, designed as clones 3 and 115, were isolated from a phage-displayed human VH antibody library. Domain-based bispecific T- cell engagers (DbTE) based on these two antibodies exhibited potent killing of uPAR-positive cancer cells. Thus, these two anti-uPAR domain antibodies are promising candidates for treating uPAR positive cancers.

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