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- W2890561829 abstract "5511 Background: We report a Phase I study of six patients with epithelial ovarian cancer treated with an intravenous infusion of autologous T cells transduced to express a chimeric antigen receptor directed against mesothelin (CART-meso). Methods: Six recurrent serous ovarian cancer patients were treated with autologous lentiviral vector transduced T cells expressing a second generation chimeric antigen receptor (CAR) construct targeting mesothelin. The CAR is composed of an extracellular anti-mesothelin single chain variable fragment derived from mouse monoclonal antibody SS1 fused to the intracellular signaling domains 4-1BB (CD137) and TCR zeta. Four patients received a single dose of 3 x 10^7 CART-meso cells/m2 and two patients received 3 x 10^8 CART-meso cells/m2, without (n = 4) or with (n = 2) lymphodepletion. Results: There were no acute AE related to the infusion and no cytokine release syndrome was experienced. Related Grade 3-4 AEs include pleural effusion, tachypnea, and dyspnea in one patient and related Grade 3 AEs include abdominal pain, ascites, and constipation in two other patients. CART-meso T cells were detectable in the peripheral blood starting 1 hour after infusion and expanded with a peak at Day 7-10 followed by a contraction phase. Higher levels were detected in patients treated with the higher dose of CART-meso cells and with lymphodepletion. Expansion of CART-meso cells was also observed in the malignant pleural effusion of one patient. Clearing of malignant cells in the pleural fluid was seen on Day 21-26 after infusion without lymphodepletion suggesting a direct anti-tumor effect. Trafficking of CART-meso cells was noted in tumor samples from three of four patients. At one month after treatment, all six patients showed stable disease on imaging per RECIST criteria. Conclusions: Phase I trial of infusion of CART-meso T cells in patients with recurrent serous ovarian cancer was found to be feasible and safe. CART-meso cells engrafted and expanded in the blood of all subjects, and trafficked to sites of tumor resulting in clearance of pleural effusion in one patient. These encouraging preliminary results may help guide future clinical trials in adoptive T cell therapy. Clinical trial information: NCT02159716." @default.
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- W2890561829 date "2016-05-20" @default.
- W2890561829 modified "2023-10-14" @default.
- W2890561829 title "Anti-mesothelin chimeric antigen receptor T cells in patients with epithelial ovarian cancer." @default.
- W2890561829 doi "https://doi.org/10.1200/jco.2016.34.15_suppl.5511" @default.
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