Frontiers in Oncology (Oct 2023)

Human antibody VH domains targeting uPAR as candidate therapeutics for cancers

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

DOI
https://doi.org/10.3389/fonc.2023.1194972
Journal volume & issue
Vol. 13

Abstract

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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.

Keywords