A modular molecular vacuum can clear out three different cancer-driving proteins at the same time while delivering a toxic payload to the cell.
Cancer cells often survive treatment by switching from one growth pathway to another. This new nanobody system, called MINDS, physically drags multiple different receptors into the cell's disposal unit to be destroyed. By targeting three pathways simultaneously, the drug leaves the cancer with no backup options for survival. The system also carries a highly potent drug that only activates once it is inside the tumor. This multi-pronged attack is millions of times more powerful than current single-target therapies in lab tests.
Multispecific nanobody degraders co-deplete membrane receptors and enable targeted delivery of diverse payloads
bioRxiv · 10.64898/2026.05.02.722401
Targeting membrane receptors underlies the success of antibody-drug conjugates (ADCs), yet single-receptor formats can be limited by heterogeneous expression, compensatory signaling, and variable internalization. Here we developed Multivalent Interchangeable Nanobody Degradation System (MINDS), a modular nanobody-Fc chassis that co-engages multiple membrane receptors, promotes their lysosomal co-depletion, and enables delivery of diverse intracellular payloads. As a proof of concept, we generate