Induction of Cytotoxic T Lymphocytes Primed with Tumor RNA-loaded Dendritic Cells in Esophageal Squamous Cell Carcinoma: Preliminary Step for DC Vaccine Design

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2010 Jun 8

PMID 20525404

Citations 12

Authors

Mehran Gholamin

Omeed Moaven

Moein Farshchian

Mahmoud Mahmoudi

Mojtaba Sankian

Bahram Memar

Mohammad Naser Forghani

Reza Malekzadeh

Mohammad Taghi Rajabi-Mashhadi

Mohammad Reza Abbaszadegan

Affiliations

Soon will be listed here.

Abstract

Background: Dendritic cells (DC) are potent antigen presenting cells with the ability to prime naïve 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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