Neoantigen in esophageal squamous cell carcinoma for dendritic cell-based cancer vaccine development

Abstract

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.

MEIS1 knockdown may promote differentiation of esophageal squamous carcinoma cell line KYSE‐30

“…In addition, deregulation of signaling pathways can induce tumorigenesis and cancer progression. Accordingly, identification of the involved genes in tumor emergence and understanding of underlying molecular mechanisms are required for representing effective therapeutic targets (Forghanifard et al, ; Patel et al, ).…”

Pilot study special AT-rich sequence-binding protein 1 investigating as a potential biomarker for esophageal squamous cell carcinoma

“…Esophageal carcinoma is a highly malignant tumor that is typically diagnosed in advanced stages due to its asymptomatic course of tumorigenesis . It is the sixth most common cause of death due to cancer, with 406 000 deaths (5.4%) worldwide annually .…”

“…Esophageal carcinoma is a highly malignant tumor that is typically diagnosed in advanced stages due to its asymptomatic course of tumorigenesis. 1 It is the sixth most common cause of death due to cancer, with 406 000 deaths (5.4%) worldwide annually. 2 There are two primary histologic types of oesophageal carcinoma, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC).…”

Treatment of Dutch rat models of glioma using EphrinA1-PE38/GM-CSF chitosan nanoparticles by in situ activation of dendritic cells

“…EphA2 is almost never expressed in various normal adult epithelial cells, but it is highly expressed in glioma-associated blood vessels [4][5][6]. Although dendritic cells (DCs) used in DCbased immunotherapy are loaded with tumor-associated antigens, the antitumor immune response is also effectively stimulated in CTLs [7,8]. Therefore, targeted killing of tumor cells without damage to normal cells can be achieved with this therapy, making it a highly promising new form of therapy.…”