CEA Plasmid as Therapeutic DNA Vaccination against Colorectal Cancer

Document Type: Original Article

Authors

1 Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Shahid Fallahi Polyclinic, AJA University of Medical Sciences, Tehran, Iran

3 Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

4 Department of biotechnology, Pasteur Institute of Iran, Tehran, Iran

5 Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Background: Human colorectal cancer cells overexpress carcinoembryonic antigen (CEA). CEA is a glycoprotein which has shown to be a promising vaccine target for immunotherapy against colorectal cancer. Objective: To design a DNA vaccine harboring CEA antigen and evaluate its effect on inducing immunity against colorectal cancer cells in tumor bearing mice. Methods: In the first step the coding sequence of the CEA was cloned into the pcDNA3.1 vector. The mice were injected with the vaccine construct and the immune responses were monitored during the experiment period. The specific IgG anti-CEA, IFN-γ, IL-2 and IL-4 were measured by ELISA and levels of IFN-γ was detected by ELISpot assay. The lymphocyte proliferation was assessed using a 5-bromo-2-deoxyuridine (BrdU) cell proliferation assay kit. Results: Immunization of the mice with the CEA plasmid resulted in stimulation of CEA-specific T cell and antibody responses. The serum level of specific IgG antibodies against CEA was increased in immunized mice. Moreover, the injection of CEA plasmid led to the stimulation of T-helper-1 by increase in the secretion of IFN-γ, IL-2 and lymphocyte proliferation response. Conclusion: As the CEA DNA vaccine displayed encouraging antitumor effects, therefore, we suggest that it can be a potential therapeutic modality for colorectal cancer and is worthy of further investigation.

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