Neoantigen in esophageal squamous cell carcinoma for dendritic cell-based cancer vaccine development
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Esophageal squamous cell carcinoma (ESCC) is a highly malignant tumor which usually is diagnosed in advanced stages due to its asymptomatic course of tumorigenesis. Current therapeutic modalities are not effective enough and the 5-year survival rate of the disease is still very low which prompts the urgent need for finding novel efficient therapeutic methods. In this study, we evaluated ex vivo immune response of ESCC patients against our newly designed chimeric construct consisting of highly immunogenic cancer-testis antigens. After confirming effective expression of the in vitro transcribed chimeric mRNA in ex vivo electroporated dendritic cells (DCs) of the ESCC patients, the patients’ CTLs were primed by DCs and cytotoxicity assay was performed to evaluate how the primed CTLs can recognize and target the chimeric mRNA-loaded cells. The chimeric protein was strongly expressed relative to the housekeeping gene expression in electroporated cells. The cytotoxicity of the CTLs was significantly higher in DCs loaded with chimeric mRNAs compared to mock DCs (p < 0.05) in all of the tested ESCC patients. We are introducing a novel construct that our functional study showed can stimulate and induce an effective immune response in ESCC patients. The designed chimeric mRNA-loaded DCs are capable of priming CTLs effectively and induce cytotoxicity against tumor. Therefore, loading DCs with chimeric epitopes of highly immunogenic antigens, such as cancer-testis antigens, are potentially interesting and effective therapeutic modalities for immunotherapy of ESCC.
KeywordsEsophageal squamous cell carcinoma Immuno-gene therapy RNA vaccine CTAs Dendritic cell Chimeric construct Cytotoxicity
The authors gratefully acknowledge the colleagues at the Departments of Surgery and Pathology in Omid, Qaem and Imam Reza hospitals of MUMS, Mashhad, for samples preparation. We are grateful to Dr. Mojtaba Sankian, Dr. Mohsen Tehrani and Ms. Maliheh Moghadam at Immunobiochemistry Lab, Immunology Research Center, Avicenna Research Institute, Mashhad, as well as our colleagues at Division of Human Genetics, for their kind help and support in technical aspects. This study was supported by the grant number 88098 from the Vice Chancellor for Research at MUMS.
Conflict of interest
The authors declare that they have no conflict of interest.
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