{"entity":{"id":"idea-mesothelin-car-t-regional","kind":"idea","name":"Regionally delivered mesothelin CAR-T with PD-1 blockade","aka":[],"tldr":"Deliver engineered T cells directly into the chest cavity where mesothelioma grows, and give immunotherapy to keep them working.","summary":"This idea would infuse mesothelin-directed CAR-T cells directly into the pleural cavity of patients with relapsed mesothelioma and add PD-1 blockade to keep the cells working. Mesothelin is expressed on almost all mesotheliomas, the pleural space is accessible, regional delivery avoids on-target lung toxicity, and in preclinical models CAR-T exhaustion is reversible with checkpoint blockade. A phase 1 study at Memorial Sloan Kettering Cancer Center led by Adusumilli combined intrapleural CAR-T with pembrolizumab and produced responses and some long survivors. The next step is a phase 2 with a second-line control and an armoured CAR-T arm; at an early clinical stage, it addresses the bottleneck of cold tumours and the idea of treating the body cavity rather than the bloodstream.","asOf":"2026-09-07","links":[{"label":"Adusumilli et al., Phase 1 trial of regional mesothelin-targeted CAR T-cell therapy with pembrolizumab in malignant pleural disease (Cancer Discovery 2021)","url":"https://doi.org/10.1158/2159-8290.CD-21-0407"}],"tags":[],"related":[],"cancers":["mesothelioma"],"sections":[],"technologies":["car-t","armored-car"],"targets":["mesothelin","pd1"],"drugs":[],"companies":[],"institutions":["mskcc"],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-adusumilli-cancer-discov","paper-mesothelin-mesothelioma-cancer-discov-2016","paper-mesothelin-mesothelioma-clin-cancer-res-2004","paper-mesothelin-mesothelioma-j-clin-oncol-2016"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Intrapleural mesothelin CAR-T plus PD-1 blockade achieves median OS beyond 24 months in relapsed mesothelioma, exceeding historical second-line outcomes.","rationale":"Mesothelin is near-universally expressed; the pleural space is accessible; CAR-T exhaustion is reversible with checkpoint blockade in preclinical models.","test":"Phase 2 with a contemporaneous control (second-line chemotherapy or nivolumab), OS endpoint; armoured (PD-1 dominant-negative) CAR-T variant as a second arm.","maturity":"early-clinical"},"route":"/ideas/idea-mesothelin-car-t-regional/","neighbours":{"cancer":[{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"}],"technology":[{"id":"armored-car","kind":"technology","name":"Armoured, logic-gated & next-gen CARs","route":"/technologies/armored-car/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"target":[{"id":"mesothelin","kind":"target","name":"Mesothelin","route":"/targets/mesothelin/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"institution":[{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"paper":[{"id":"paper-adusumilli-cancer-discov","kind":"paper","name":"A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti-PD-1 Agent Pembrolizumab","route":"/key-papers/paper-adusumilli-cancer-discov/"},{"id":"paper-mesothelin-mesothelioma-j-clin-oncol-2016","kind":"paper","name":"Mesothelin Immunotherapy for Cancer: Ready for Prime Time?","route":"/key-papers/paper-mesothelin-mesothelioma-j-clin-oncol-2016/"},{"id":"paper-mesothelin-mesothelioma-cancer-discov-2016","kind":"paper","name":"Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors","route":"/key-papers/paper-mesothelin-mesothelioma-cancer-discov-2016/"},{"id":"paper-mesothelin-mesothelioma-clin-cancer-res-2004","kind":"paper","name":"Mesothelin: a new target for immunotherapy","route":"/key-papers/paper-mesothelin-mesothelioma-clin-cancer-res-2004/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"}],"idea":[{"id":"idea-bio2-intracavitary-immunotherapy","kind":"idea","name":"Treat the body cavity, not the bloodstream, for surface spread","route":"/ideas/idea-bio2-intracavitary-immunotherapy/"}]}}