{"entity":{"id":"idea-bio2-intraventricular-car-t","kind":"idea","name":"Deliver CAR-T cells straight into the fluid around the brain","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (The brain: barrier and sanctuary): Stupp et al., Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma (NEJM 2005)","url":"https://doi.org/10.1056/NEJMoa043330"}],"tags":[],"related":[],"cancers":["breast-her2-positive","glioblastoma"],"sections":[],"technologies":["car-t","glioma-car-t"],"targets":["her2","b7h3"],"drugs":[],"companies":[],"institutions":["city-of-hope"],"pathways":[],"terms":["her2-brain-metastases","crs"],"trials":[],"people":[],"bottlenecks":["b-brain-delivery","b-metastasis-biology"],"keyPapers":["paper-slamon-her2-breast-ovarian-science-1989","paper-yarden-sliwkowski-erbb-network-nrmcb-2001"],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"medium","horizonYears":5},"route":"/ideas/idea-bio2-intraventricular-car-t/","neighbours":{"cancer":[{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"},{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"glioma-car-t","kind":"technology","name":"CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)","route":"/technologies/glioma-car-t/"}],"target":[{"id":"b7h3","kind":"target","name":"B7-H3","route":"/targets/b7h3/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"institution":[{"id":"city-of-hope","kind":"institution","name":"City of Hope","route":"/institutions/city-of-hope/"}],"term":[{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"her2-brain-metastases","kind":"term","name":"HER2-positive brain metastases","route":"/terms/her2-brain-metastases/"}],"bottleneck":[{"id":"b-metastasis-biology","kind":"bottleneck","name":"Metastasis is understood least and studied last","route":"/bottlenecks/b-metastasis-biology/"},{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"}],"paper":[{"id":"paper-slamon-her2-breast-ovarian-science-1989","kind":"paper","name":"Slamon 1989: HER2/neu in human breast and ovarian cancer","route":"/key-papers/paper-slamon-her2-breast-ovarian-science-1989/"},{"id":"paper-yarden-sliwkowski-erbb-network-nrmcb-2001","kind":"paper","name":"Yarden and Sliwkowski 2001: untangling the ErbB signalling network","route":"/key-papers/paper-yarden-sliwkowski-erbb-network-nrmcb-2001/"}]}}