ProTCE-PSMA

ProTCE-PSMA is a conditionally activated T-cell engager (TCE) prodrug targeting Prostate-Specific Membrane Antigen (PSMA) and CD3, developed by Biocytogen. Designed using a tumor microenvironment (TME) conditionally activated platform, the molecule is engineered to overcome common TCE challenges such as cytokine release syndrome (CRS) and on-target off-tumor toxicity. Its architecture includes a high-affinity VHH antibody for PSMA, a proprietary CD3 binder, a CD3 masking peptide, a TME-cleavable linker, and an anti-human serum albumin (HSA) single-domain antibody (sdAb) for pharmacokinetic (PK) modulation. The scFv-free format reduces steric hindrance, enhancing binding affinity. In the tumor microenvironment, enzymes cleave the linker to release the CD3 mask, enabling localized T-cell activation. ProTCE-PSMA features a "PK switch" property, where the prodrug form has a long half-life (approximately 5 days in cynomolgus monkeys) while the active form is rapidly cleared (half-life of 1 day), significantly improving the therapeutic index and safety profile compared to conventional TCEs.