Next Generation Immunotherapy for Pancreatic Cancer: DNA Vaccination is Seeking New Combo Partners

Cancers
Paola CappelloFrancesco Novelli

Abstract

Pancreatic Ductal Adenocarcinoma (PDA) is an almost incurable radio- and chemo-resistant tumor, and its microenvironment is characterized by a strong desmoplastic reaction associated with a significant infiltration of T regulatory lymphocytes and myeloid-derived suppressor cells (Tregs, MDSC). Investigating immunological targets has identified a number of metabolic and cytoskeletal related molecules, which are typically recognized by circulating antibodies. Among these molecules we have investigated alpha-enolase (ENO1), a glycolytic enzyme that also acts a plasminogen receptor. ENO1 is also recognized by T cells in PDA patients, so we developed a DNA vaccine that targets ENO1. This efficiently induces many immunological processes (antibody formation and complement-dependent cytotoxicity (CDC)-mediated tumor killing, infiltration of effector T cells, reduction of infiltration of myeloid and Treg suppressor cells), which significantly increase the survival of genetically engineered mice that spontaneously develop pancreatic cancer. Although promising, the ENO1 DNA vaccine does not completely eradicate the tumor, which, after an initial growth inhibition, returns to proliferate again, especially when Tregs and MDSC ensue in the t...Continue Reading

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Citations

Sep 22, 2019·International Journal of Molecular Sciences·Bilikis Aderonke AbolarinwaYen-Hua Huang
Sep 1, 2018·Epigenomes·Claudia C Preston, Randolph S Faustino
Dec 2, 2020·Journal of Experimental & Clinical Cancer Research : CR·Lidong CaoRanji Cui
Feb 16, 2021·Frontiers in Genetics·Frankis A AlmaguelCarlos A Casiano
Jun 25, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Clara S MundryKamiya Mehla
May 11, 2021·World Journal of Clinical Cases·Jai Hoon YoonSung-Hoon Moon

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Datasets Mentioned

BETA
GM-CSF

Clinical Trials Mentioned

NCT02637531
NCT02159716
NCT01583686
NCT01897415
NCT02580747
NCT02465983
NCT02349724
NCT02416466
NCT02587689
NCT02988960

Software Mentioned

ENOblock
SERological Proteome Analysis ( SERPA )

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