کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8726335 | 1590025 | 2018 | 4 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Activity of Mesothelin-Specific Chimeric Antigen Receptor T Cells Against Pancreatic Carcinoma Metastases in a Phase 1 Trial
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کلمات کلیدی
mRNAMAVFDGmessenger RNA - RNA messengerPancreatic ductal adenocarcinoma - آدنوکارسینوم پانکراس داکتالPDAC یا pancreatic ductal adenocarcinoma - آدنوکارسینومای داکتال پانکراسAntitumor immunity - ایمنی ضد تومورinterleukin - اینترلوکینImmune therapy - درمان ایمنیCAR - ماشینchimeric antigen receptor - گیرنده آنتی ژنهای کرومیک
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 155, Issue 1, July 2018, Pages 29-32
Journal: Gastroenterology - Volume 155, Issue 1, July 2018, Pages 29-32
نویسندگان
Gregory L. Beatty, Mark H. O'Hara, Simon F. Lacey, Drew A. Torigian, Farzana Nazimuddin, Fang Chen, Irina M. Kulikovskaya, Michael C. Soulen, Maureen McGarvey, Anne Marie Nelson, Whitney L. Gladney, Bruce L. Levine, J. Joseph Melenhorst,