# Open the barrier so engineered immune cells can enter the brain

Source: https://onco.cc/ideas/idea-bio2-fus-for-cell-entry/  
OnCo record `idea-bio2-fus-for-cell-entry` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Engineered immune cells given by drip rarely reach brain tumours. Briefly opening the barrier with focused ultrasound at the right moment may let them in.

## Summary

Most focused ultrasound work has aimed at small molecules and antibodies, but preclinical studies show increased trafficking of natural killer cells and CAR-T cells into brain tumours after sonication. Timing matters because the barrier reseals within hours, so the infusion schedule must be matched to the opening window.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Sonication immediately before or during cell infusion increases intratumoural engineered cell density in the brain by at least fivefold compared with infusion alone, measurable by imaging or by post-mortem and resection tissue analysis.
- Rationale: Cell therapy in brain tumours currently requires direct intratumoural or intraventricular delivery, which limits repeat dosing. If systemic infusion could be made to work, cell therapy in the brain would become far more practical.
- Proposed test: Large-animal or first-in-human study pairing radiolabelled or reporter-gene-tagged cell infusion with and without sonication, quantifying brain cell delivery as the primary endpoint.
- Maturity: preclinical-evidence
- Actor: research

## Sources

- Bottleneck evidence (The brain: barrier and sanctuary): Stupp et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma (NEJM 2005): https://doi.org/10.1056/NEJMoa043330

## Connected records

- cancers: [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/)
- technologies: [CAR-NK & CAR-macrophage](https://onco.cc/technologies/car-nk-macrophage/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)](https://onco.cc/technologies/glioma-car-t/), [Focused-ultrasound blood-brain barrier opening](https://onco.cc/technologies/bbb-focused-ultrasound/), [Immuno-PET](https://onco.cc/technologies/immuno-pet/)
- targets: [B7-H3](https://onco.cc/targets/b7h3/), [GD2 (disialoganglioside)](https://onco.cc/targets/gd2/)
- companies: [Insightec](https://onco.cc/companies/insightec/)
- bottlenecks: [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/), [The brain: barrier and sanctuary](https://onco.cc/bottlenecks/b-brain-delivery/)

---
JSON: https://onco.cc/api/v1/entities/idea-bio2-fus-for-cell-entry.json