OnCo
ideasIdea

Focused-ultrasound BBB opening to deliver ADCs and radioligands to glioma

Brain tumours have targets that ADCs could hit, but antibodies cannot cross the barrier. Open the barrier with ultrasound first.

Depatuxizumab mafodotin (EGFR ADC) failed in INTELLANCE-1 partly through poor CNS penetration. Focused ultrasound raises antibody delivery several-fold in humans (Insightec, Carthera trials). Combining BBB opening with EGFR/EGFRvIII or B7-H3 ADCs, or with 177Lu/225Ac radioconjugates, is untested clinically.

Confidence
10%–30%likelyOnCo editors (initial estimate), 2026-09-07 · BBB-opening is feasible; drug efficacy in glioblastoma has a long record of failure.
Hypothesis
Opening the blood-brain barrier with focused ultrasound immediately before ADC or radioconjugate infusion achieves therapeutic intratumoural concentrations and objective responses in recurrent glioblastoma.
Rationale
Mechanism-agnostic delivery boost; targets (EGFR, B7-H3, IL13Rα2) are validated; payload potency compensates for limited volume.
What would test it
Phase 1 with paired pre/post-opening tumour sampling at re-resection measuring ADC concentration; expansion cohort with RANO response.
Maturity
preclinical evidence

Connected

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cancers

1
Glioma & glioblastoma

technologies

3
Antibody-drug conjugate (ADC)Focused-ultrasound blood-brain barrier openingRadio-antibody & radio-ADC

targets

2
B7-H3EGFR

terms

1
Blood-brain barrier (BBB)

ideas

1
A skull ultrasound implant that opens the barrier at every cycle

bottlenecks

1
The brain: barrier and sanctuary