# Deliver CAR-T cells straight into the fluid around the brain

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

## TL;DR

Cancer spreading along the linings of the brain has no treatment that reliably controls it. Injecting engineered immune cells directly into the brain fluid, through a small reservoir, reaches it.

## Summary

Intraventricular delivery of HER2-directed CAR-T cells via an Ommaya reservoir has produced responses in leptomeningeal metastasis in early trials at City of Hope, and intrathecal chemotherapy is long-established. Local delivery avoids the barrier entirely, gives high local cell dose and appears to reduce systemic cytokine toxicity.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Repeat intraventricular CAR-T dosing produces cerebrospinal fluid tumour cell clearance in at least a third of patients with leptomeningeal metastasis, with median survival better than the current two to four months.
- Rationale: The cerebrospinal fluid is a closed, low-volume compartment where a small number of cells produces high effective concentration, and cell products can be re-dosed through an implanted reservoir without repeated surgery.
- Proposed test: A multi-centre phase 2 in HER2-positive breast cancer leptomeningeal disease with cerebrospinal fluid cytology and ctDNA clearance as primary endpoints, and quality of life measured throughout.
- Maturity: early-clinical
- Actor: clinic

## 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/), [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/)
- technologies: [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/)
- targets: [B7-H3](https://onco.cc/targets/b7h3/), [HER2](https://onco.cc/targets/her2/)
- institutions: [City of Hope](https://onco.cc/institutions/city-of-hope/)
- terms: [Cytokine release syndrome (CRS)](https://onco.cc/terms/crs/), [HER2-positive brain metastases](https://onco.cc/terms/her2-brain-metastases/)
- bottlenecks: [Metastasis is understood least and studied last](https://onco.cc/bottlenecks/b-metastasis-biology/), [The brain: barrier and sanctuary](https://onco.cc/bottlenecks/b-brain-delivery/)
- key papers: [Slamon 1989: HER2/neu in human breast and ovarian cancer](https://onco.cc/key-papers/paper-slamon-her2-breast-ovarian-science-1989/), [Yarden and Sliwkowski 2001: untangling the ErbB signalling network](https://onco.cc/key-papers/paper-yarden-sliwkowski-erbb-network-nrmcb-2001/)

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