The next generation DNA vaccine ENO3PEP induces effector T cell responses and promotes anti-tumor immunity in pancreatic cancer.

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B139
Abstract ID: 4604

Presenting Author:
Silvia Brugiapaglia , PhD student at Univ. degli Studi di Torino

Abstract:

Pancreatic ductal adenocarcinoma (PDA) remains one of the deadliest cancer due to the absence of symptoms in most of localized disease, the paucity of diagnostic biomarkers for earlier stage tumors and the difficult-to-access anatomical location of the pancreas for an efficient prevention screening. Despite many efforts, they have not translated into a breakthrough in clinical care. ENO3PEP DNA vaccine aims to generate anti-tumor immune response directed against the most immunogenic epitopes of the PDA associated antigen alpha-enolase (ENO1). Genetically engineered mice that spontaneously develop PDA (KPC model) were vaccinated for a total of four rounds. ENO3PEP significantly reduced pancreatic cancer lesions and metastasis in lung and liver. ENO3PEP enhanced the humoral response increasing the production of anti-ENO1 IgG antibodies since the first round of vaccination and, of note, boosted the production of anti-ENO1 IgG2c antibodies whose presence is improved by Th1 cells. Relative to cellular response, ENO3PEP raised the secretion of IFN-γ by T cells stimulated with ENO1 or syngeneic tumor cells. Notably, ENO3PEP had an impact on tumor microenvironment composition as it decreased collagen deposition, recruited more effector immune cells (CD4⁺ T cells, CD8⁺ T cells, M1 macrophages) and decreased suppressive ones (FoxP3⁺ T cells, M2 macrophages) at tumor site. The ENO3PEP vaccine emerged as potential vaccine suitable for immunotherapy in pancreatic cancer.