@article {Katze001097, author = {Steven C Katz and Ashley E Moody and Prajna Guha and John C Hardaway and Ethan Prince and Jason LaPorte and Mirela Stancu and Jill E Slansky and Kimberly R Jordan and Richard D Schulick and Robert Knight and Abdul Saied and Vincent Armenio and Richard P Junghans}, title = {HITM-SURE: Hepatic immunotherapy for metastases phase Ib anti-CEA CAR-T study utilizing pressure enabled drug delivery}, volume = {8}, number = {2}, elocation-id = {e001097}, year = {2020}, doi = {10.1136/jitc-2020-001097}, publisher = {BMJ Specialist Journals}, abstract = {In recent years, cell therapy technologies have resulted in impressive results in hematologic malignancies. Treatment of solid tumors with chimeric antigen receptor T-cells (CAR-T) has been less successful. Solid tumors present challenges not encountered with hematologic cancers, including high intra-tumoral pressure and ineffective CAR-T trafficking to the site of disease. Novel delivery methods may enable CAR-T therapies for solid tumor malignancies. A patient with liver metastases secondary to pancreatic adenocarcinoma received CAR-T targeting carcinoembryonic antigen (CEA). Previously we reported that Pressure-Enabled Drug Delivery (PEDD) enhanced CAR-T delivery to liver metastases 5.2-fold. Three doses of anti-CEA CAR-T were regionally delivered via hepatic artery infusion (HAI) using PEDD technology to optimize the therapeutic index. Interleukin-2 was systemically delivered by continuous intravenous infusion to support CAR-T in vivo. HAI of anti-CEA CAR-T was not associated with any serious adverse events (SAEs) above grade 3 and there were no on-target/off-tumor SAEs. Following CAR-T treatment, positron emission tomography-CT demonstrated a complete metabolic response within the liver, which was durable and sustained for 13 months. The response was accompanied by normalization of serum tumor markers and an abundance of CAR+ cells found within post-treatment tumor specimens. The findings from this report exhibit biologic activity and safety of regionally infused CAR-T for an indication with limited immune-oncology success to date. Further studies will determine how HAI of CAR-T may be included in multidisciplinary treatment plans for patients with liver metastases. ClinicalTrials.gov number, NCT02850536.}, URL = {https://jitc.bmj.com/content/8/2/e001097}, eprint = {https://jitc.bmj.com/content/8/2/e001097.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }