Activity of Mesothelin-Specific Chimeric Antigen Receptor T Cells Against Pancreatic Carcinoma Metastases in a Phase 1 Trial

作者：Beatty, Gregory L.^*; O'Hara, Mark H.; Lacey, Simon F.; Torigian, Drew A.; Nazimuddin, Farzana; Chen, Fang; Kulikovskaya, Irina M.; Soulen, Michael C.; McGarvey, Maureen; Nelson, Anne Marie; Gladney, Whitney L.; Levine, Bruce L.; Melenhorst, J. Joseph; Plesa, Gabriela; June, Carl H.

来源：Gastroenterology, 2018, 155(1): 29-32.

DOI：10.1053/j.gastro.2018.03.029

• Immune Response Heterogeneity
• Immune Therapy
• Antitumor Immunity
• Pancreatic Cancer Treatment

Pancreatic ductal adenocarcinoma (PDAC) is resistant to T-cell-mediated immunotherapy. We engineered T cells to transiently express a messenger RNA encoding a chimeric antigen receptor (CAR) specific for mesothelin, a protein that is overexpressed by PDAC cells. We performed a phase I study to evaluate the safety and efficacy of adoptive cell therapy with autologous mesothelin-specific CAR T cells (CARTmeso cells) in 6 patients with chemotherapy-refractory metastatic PDAC. Patients were given intravenous CARTmeso cells 3 times weekly for 3 weeks. None of the patients developed cytokine release syndrome or neurologic symptoms and there were no dose-limiting toxicities. Disease stabilized in 2 patients, with progression-free survival times of 3.8 and 5.4 months. We used F-18-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computed tomography imaging to monitor the metabolic active volume (MAV) of individual tumor lesions. The total MAV remained stable in 3 patients and decreased by 69.2% in 1 patient with biopsy-proven mesothelin expression; in this patient, all liver lesions had a complete reduction in FDG uptake at 1 month compared with baseline, although there was no effect on the primary PDAC. Transient CAR expression was detected in patients' blood after infusion and led to expansion of new immunoglobulin G proteins. Our results provide evidence for the potential antitumor activity of messenger RNA CARTmeso cells, as well as PDAC resistance to the immune response.

• 出版日期2018-7