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

Source: https://onco.cc/ideas/idea-fus-plus-adc-glioma/  
OnCo record `idea-fus-plus-adc-glioma` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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

## Summary

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-06
- 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.
- Proposed test: Phase 1 with paired pre/post-opening tumour sampling at re-resection measuring ADC concentration; expansion cohort with RANO response.
- Maturity: preclinical-evidence

## Sources

- Sonabend et al., Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in glioblastoma (Lancet Oncology 2023): https://doi.org/10.1016/S1470-2045(23)00112-2

## Connected records

- cancers: [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Focused-ultrasound blood-brain barrier opening](https://onco.cc/technologies/bbb-focused-ultrasound/), [Radio-antibody & radio-ADC](https://onco.cc/technologies/radioimmunotherapy/)
- targets: [B7-H3](https://onco.cc/targets/b7h3/), [EGFR](https://onco.cc/targets/egfr/)
- terms: [Blood-brain barrier (BBB)](https://onco.cc/terms/blood-brain-barrier/)
- key papers: [B7-H3 in Brain Malignancies: Immunology and Immunotherapy](https://onco.cc/key-papers/paper-b7-h3-glioblastoma-int-j-biol-sci-2023/), [Emerging functions of the EGFR in cancer](https://onco.cc/key-papers/paper-egfr-glioblastoma-mol-oncol-2018/), [Oncogenic EGFR signaling networks in glioma](https://onco.cc/key-papers/paper-egfr-glioblastoma-sci-signal-2009/), [Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial](https://onco.cc/key-papers/paper-sonabend-lancet-oncol/)
- bottlenecks: [The brain: barrier and sanctuary](https://onco.cc/bottlenecks/b-brain-delivery/)
- ideas: [A skull ultrasound implant that opens the barrier at every cycle](https://onco.cc/ideas/idea-bio2-implanted-ultrasound-repeat-dosing/)

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