Induction of cytotoxic T lymphocytes primed with Tumor RNA-loaded Dendritic Cells in esophageal squamous cell carcinoma: preliminary step for DC vaccine design
By: Mehran Gholamin , Omeed Moaven , Moein Farshchian , Mahmoud Mahmoudi , Mojtaba Sankian , Bahram Memar , Mohammad Naser Forghani , Reza Malekzadeh , Mohammad Taghi Rajabi-Mashhadi and Mohammad REZA Abbaszadegan

BMC Cancer 2010, 10:261 doi:10.1186/1471-2407-10-261
Published: 7 June 2010

Abstract (Provisional)

Background

Dendritic Cells (DC) are potent antigen presenting cells with the ability to prime naive T cells and convert them to cytotoxic T-lymphocytes (CTL). We evaluated the capability of autologous DCs transfected with total tumor and normal RNA to induce cytotoxic CTL as the preliminary step to design a DC-based vaccine in the esophageal squamous cell carcinoma (ESCC).

Methods

Monocytes-derived DCs were electroporated with either total tumor RNA or normal RNA. T cells were then primed with tumor RNA transfected DCs and lytic effects of the generated CTL were measured with Cytotoxicity assay and IFN-gamma Release Elispot assay.

Results

Cytotoxicity was induced against DCs loaded with tumoral RNA (%24.8+/-5.2 SEM) while in normal RNA-loaded DCs, it was minimal (%6.1+/-2.4 SEM) and significantly lower (p < 0.05). INF-gamma secretion was more than 2-folds higher in tumoral RNA-loaded DCs when compared with normal RNA-loaded DCs (p < 0.05).

Conclusion

Electroporating DCs with tumor RNA generated tumor antigen presenting cells which in turn enhanced cytotoxic effects of the T cells against ESCC. This may be a useful autologous ex vivo screening tool for confirming the lytic effects of primed T cells on tumors and evaluate probable further adverse effects on noncancerous tissues. These data provide crucial preliminary information to establish a total tumor RNA-pulsed DC vaccine therapy of ESCC.

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* Albert Einstein College of Medicine has been
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