CEA promoter-regulated oncolytic adenovirus-mediated Hsp70 expression in immune gene therapy for pancreatic cancer

Abstract

Gene therapy is an important means for the comprehensive treatment of pancreatic cancer. Challenges associated with gene therapy include control of vector security and effective genetic screening. In this paper, a CEA promoter-regulated oncolytic adenovirus vector was constructed. The reporter gene assay demonstrated that the viral vector was confirmed to have tumor-specific replication features. In vitro cytology studies showed that the CEA promoter regulated the proliferation of the adenovirus vector carrying the Hsp70 gene (AdCEAp-Hsp70), which significantly increased the expression levels of Hsp70 in the CEA-positive pancreatic cancer cells, resulting in an overall reduction in the survival of cancer cells. In the human pancreatic cancer Panc-1 xenograft model in immune deficient nude mice, the CEA promoter-regulated adenovirus AdCEAp-Hsp70 significantly inhibited tumor growth. In the rat pancreatic cancer DSL-6A/C1 xenograft model in rats, the viral proliferation and high expression levels of Hsp70 promoted the interstitial infiltration of CD4+, CD8+ and gamma/delta T cells into tumors, induced host secretion of the cytokines TGF-β, INF-γ, and IL-6 and had a dual anti-tumor effects that completely inhibited the growth of pancreatic cancer. The results demonstrated that the oncolytic adenovirus under the control of CEA promoter provides additional assurances regarding the safety and efficiency of cancer gene therapy. This gene therapy model improves anti-cancer efficiency and has broad applications and developmental prospects.