Multispecific theranostic nano-engager platform

Objetivo

"This ERC Proof of Concept proposal develops ""Nano-BITE,"" a multifunctional nanoparticle platform addressing limitations of current cancer immunotherapy. Existing bispecific antibodies like blinatumomab suffer from rapid kidney clearance due to small molecular size, requiring continuous intravenous infusion for weeks and showing poor efficacy in solid tumors. The Nano-BITE platform uses PLGA nanoparticles as scaffolds incorporating four integrated features: modular E3/K3 peptide chemistry enabling rapid attachment of nanobodies targeting NK cells and tumor antigens, extended circulation achieving greater than 24-hour half-life versus 7 hours for conventional engagers, localized IL-15 delivery for sustained NK cell activation within tumors without systemic toxicity, and integrated radioisotope chelators enabling PET imaging to track drug distribution and predict response. The platform's innovative ""plug-and-play"" design allows rapid adaptation to different cancers by swapping targeting modules within hours rather than 18-24 months required for new drug development. When imaging reveals antigen switching, subsequent doses can target different antigens using the same nanoparticle backbone. The 18-month validation plan includes optimizing formulation and demonstrating superior NK cell activation in vitro, followed by proving therapeutic efficacy in humanized mouse models of HER2-positive breast cancer. This approach could transform cancer immunotherapy from static treatments to dynamic platforms adapting to disease evolution, potentially capturing markets exceeding fifty billion dollars versus one to five billion for individual bispecifics."