AUTHOR=Chu Xiaojie , Li Wei , Hines Margaret G. , Lyakhov Ilya , Mellors John W. , Dimitrov Dimiter S. TITLE=Human antibody VH domains targeting uPAR as candidate therapeutics for cancers JOURNAL=Frontiers in Oncology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1194972 DOI=10.3389/fonc.2023.1194972 ISSN=2234-943X 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.