Spatially-Restricted T-Cell Engagement via Protease-Unmasking (Pro-BiTEs) White Paper

This white paper proposes the development of a platform for Protease-Activated Bispecific T-Cell Engagers (Pro-BiTEs). The platform is based on a recombinant fusion protein designed as an inert prodrug in systemic circulation, activating exclusively within the Tumor Microenvironment (TME). The core innovation is a multi-domain "ABD-Mask-Linker" architecture that incorporates a Triple-Lock activation logic (dual-protease + pH-dependency) to maximize tumor specificity and minimize on-target/off-tumor toxicity. This program directly addresses the fundamental limitations of conventional BiTEs: rapid renal clearance, systemic cytokine release syndrome, and damage to healthy tissues expressing the target antigen.The creation of a proprietary library of protease-sensitive linkers, validated against patient-derived proteases from North African cohorts should be a valuable IP for Morocco. Establishing it as the developer of high-value, conditionally-active biologic components.