Ermelinda Damko, Sr. Scientist at Regeneron, shared a post on LinkedIn:
“Most ‘dual targeting’ ADC stories still treat the second antigen as an additive feature: one more binding site on an otherwise familiar scaffold.
The HER2×EGFR click work does something qualitatively different. It uses bioorthogonal chemistry to deliberately reconfigure receptor architecture in vivo and then treats the tumor as a dynamic system to be watched, not a static target to be hit.
By covalently assembling HER2 and EGFR directed species into new complexes across HER2 high, HER2 low, EGFR high and refractory tumors, the study can ask a much sharper mechanistic question:
When we force receptors into defined configurations, shared clusters, coordinated internalization routes, extended microdomains, do we truly change payload flux into lysosomes and across heterogeneous tumor territory, or do we simply redistribute binding at the surface without touching the biology that determines response?
This article takes that question as its starting point and follows it all the way through, from the formation of click assembled multimers, to altered uptake and co internalization, to payload delivery in HER2 low and resistant disease, and finally to what it would mean to treat receptor systems, not individual antigens, as the real unit of design for the next generation of multispecific ADCs.”
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