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Gastroenterology. 2018 Jul;155(1):29-32. doi: 10.1053/j.gastro.2018.03.029. Epub 2018 Mar 20.

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

Author information

1
Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: gregory.beatty@uphs.upenn.edu.
2
Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
3
Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
4
Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
5
Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
6
Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Abstract

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 18F-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.

KEYWORDS:

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

PMID:
29567081
PMCID:
PMC6035088
[Available on 2019-07-01]
DOI:
10.1053/j.gastro.2018.03.029
[Indexed for MEDLINE]

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