{"entity":{"id":"idea-fus-plus-adc-glioma","kind":"idea","name":"Focused-ultrasound BBB opening to deliver ADCs and radioligands to glioma","aka":[],"tldr":"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.","asOf":"2026-09-06","links":[{"label":"Sonabend et al., Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in glioblastoma (Lancet Oncology 2023)","url":"https://doi.org/10.1016/S1470-2045(23)00112-2"}],"tags":[],"related":[],"cancers":["glioblastoma"],"sections":[],"technologies":["bbb-focused-ultrasound","adc","radioimmunotherapy"],"targets":["egfr","b7h3"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["blood-brain-barrier"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-sonabend-lancet-oncol","paper-egfr-glioblastoma-mol-oncol-2018","paper-egfr-glioblastoma-sci-signal-2009","paper-b7-h3-glioblastoma-int-j-biol-sci-2023"],"journals":[],"dependsOn":[],"notes":[],"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.","test":"Phase 1 with paired pre/post-opening tumour sampling at re-resection measuring ADC concentration; expansion cohort with RANO response.","maturity":"preclinical-evidence"},"route":"/ideas/idea-fus-plus-adc-glioma/","neighbours":{"cancer":[{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"},{"id":"bbb-focused-ultrasound","kind":"technology","name":"Focused-ultrasound blood-brain barrier opening","route":"/technologies/bbb-focused-ultrasound/"},{"id":"radioimmunotherapy","kind":"technology","name":"Radio-antibody & radio-ADC","route":"/technologies/radioimmunotherapy/"}],"target":[{"id":"b7h3","kind":"target","name":"B7-H3","route":"/targets/b7h3/"},{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"}],"term":[{"id":"blood-brain-barrier","kind":"term","name":"Blood-brain barrier (BBB)","route":"/terms/blood-brain-barrier/"}],"paper":[{"id":"paper-b7-h3-glioblastoma-int-j-biol-sci-2023","kind":"paper","name":"B7-H3 in Brain Malignancies: Immunology and Immunotherapy","route":"/key-papers/paper-b7-h3-glioblastoma-int-j-biol-sci-2023/"},{"id":"paper-egfr-glioblastoma-mol-oncol-2018","kind":"paper","name":"Emerging functions of the EGFR in cancer","route":"/key-papers/paper-egfr-glioblastoma-mol-oncol-2018/"},{"id":"paper-egfr-glioblastoma-sci-signal-2009","kind":"paper","name":"Oncogenic EGFR signaling networks in glioma","route":"/key-papers/paper-egfr-glioblastoma-sci-signal-2009/"},{"id":"paper-sonabend-lancet-oncol","kind":"paper","name":"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","route":"/key-papers/paper-sonabend-lancet-oncol/"}],"bottleneck":[{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"}],"idea":[{"id":"idea-bio2-implanted-ultrasound-repeat-dosing","kind":"idea","name":"A skull ultrasound implant that opens the barrier at every cycle","route":"/ideas/idea-bio2-implanted-ultrasound-repeat-dosing/"}]}}