Anti-PSMA/CD3 Protease-activated T-cell Engager JANX007

A protease-activated, masked T-cell engager (TCE) composed of a prostate-specific membrane antigen (PSMA)-binding domain and a CD3-binding domain conjugated, via a tumor protease-cleavable linker, to a peptide mask that prevents CD3 engagement on T-cells and an albumin-binding domain that extends circulating half-life, with potential immunomodulating and antineoplastic activities. Upon intravenous administration of anti-PSMA/CD3 protease-activated TCE JANX007, the tumor protease-cleavable linker is proteolytically cleaved in the tumor microenvironment (TME), which separates the active PSMA-targeted TCE from the peptide mask and the albumin-binding domain. The PSMA-binding domain targets and binds to PSMA expressed on tumor cells. The CD3-binding domain targets and binds to T-cells. The resulting cross-linkage may trigger a potent cytotoxic T-lymphocyte (CTL) response against PSMA-expressing tumor cells in the TME. PSMA, a tumor-associated antigen (TAA) and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells as well as a variety of other solid tumors. The peptide mask allows specific activation of JANX007 in the TME, thereby minimizing systemic toxicity and increasing efficacy.