ABSTRACT
Objective: To investigate the specific cytotoxicity of MUC1-specific chimeric antigen receptor (CAR)-engineered Jurkat T cells against hepatocellular carcinoma (HCC) cells. Methods: The expression cassettes of both the first and the third generation MUC1-specific CAR gene (i.e. MUC1-CAR and G3MUC1-CAR) were constructed and cloned into lentivirus transfer plasmids, respectively. Then the obtained recombinant lentiviruses carrying the MUC1-specific CAR gene and hrGFP reporter genes were used to infect Jurkat T cells in vitro to establish MUC1-sepcific CAR-engineered Jurkat cells (i.e. CAR-T cells). Subsequently, the assays of CCK-8, ELISA, and LDH were used to detect the cell proliferation, IL-2 secretion and killing effect of the CAR-T cells, respectively. Results: We successfully constructed the expression cassettes of MUC1-sepcific CAR gene and the corresponding recombinant lentivirus, established the MUC1-specific CAR-engineered Jurkat T cells. Both types of MUC1-specific CARs-engineered Jurkat T cells could recognize MUC1 molecule and specifically kill MUC1 over-expressed HCC cells while left normal hepatic cells almost undamaged. In addition, the cell proliferation, the secretion of IL-2 and killing effect of the G3MUC1-CAR-engineered Jurkat T cells was significantly superior to the MUC1-CAR-engineered counterpart (P<0.05 or 0.01). Conclusion: The MUC1-sepcific CAR-engineered Jurkat T cells can specifically kill MUC1 over-expressed HCC cells.
ABSTRACT
<p><b>BACKGROUND</b>Carcinoma of unknown primary (CUP) encompasses a heterogeneous group of tumors with varying clinical features. The management of patients of CUP remains a clinical challenge. The purpose of this study was to evaluate the clinical applications of integrated (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) information in patients with CUP, including detecting the occult primary tumor and effecting on disease therapy.</p><p><b>METHODS</b>One hundred and forty-nine patients with histologically-proven metastases of CUP were included. For all patients, the conventional diagnostic work-up was unsuccessful in localizing the primary site. Whole-body PET/CT images were obtained approximately 60 minutes after intravenous injection of 350 - 425 MBq of (18)F-FDG.</p><p><b>RESULTS</b>In 24.8% of patients, FDG PET/CT detected primary tumors that were not apparent after conventional workup. In this group of patients, the overall sensitivity, specificity, and accuracy rates of FDG PET/CT in detecting unknown primary tumors were 86.0%, 87.7%, and 87.2%, respectively. FDG PET/CT imaging also led to the detection of previously unrecognized metastases in 29.5% of patients. Forty-seven (31.5%, 47 of 149) patients underwent a change in therapeutic management.</p><p><b>CONCLUSIONS</b>FDG PET/CT is a valuable tool in patients with CUP, because it assisted in detecting unknown primary tumors and previously unrecognized distant metastases, and optimized the management of these patients.</p>