Human antibody VH domains targeting uPAR as candidate therapeutics for cancers

Xiaojie Chu; Wei Li; Margaret G Hines; Ilya Lyakhov; John W Mellors; Dimiter S Dimitrov

doi:10.3389/fonc.2023.1194972

Human antibody V_H domains targeting uPAR as candidate therapeutics for cancers

Front Oncol. 2023 Oct 9:13:1194972. doi: 10.3389/fonc.2023.1194972. eCollection 2023.

Authors

Xiaojie Chu¹, Wei Li¹, Margaret G Hines¹, Ilya Lyakhov², John W Mellors^{1

3}, Dimiter S Dimitrov^{1

3}

Affiliations

¹ Center for Antibody Therapeutics, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh Medical School, Pittsburgh, PA, United States.
² Comp IL, LLC, Carnegie, PA, United States.
³ Abound Bio, Pittsburgh, PA, United States.

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 V_H domain antibody candidates, designed as clones 3 and 115, were isolated from a phage-displayed human V_H 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.

Keywords: DbTE (domain based bispecific T cell engager); VH domain; cancer; human uPAR; therapeutic antibody.

Grants and funding

This work was supported by the UPMC.