BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDA) is an aggressive tumor, and patients typically present with late-stage disease; rates of 5-year survival after pancreaticoduodenectomy are low. Antibodies against α-enolase (ENO1), a glycolytic enzyme, are detected in more than 60% of patients with PDA, and ENO1-specific T cells inhibit the growth of human pancreatic xenograft tumors in mice. We investigated whether an ENO1 DNA vaccine elicits antitumor immune responses and prolongs survival of mice that spontaneously develop autochthonous, lethal pancreatic carcinomas. METHODS: We injected and electroporated a plasmid encoding ENO1 (or a control plasmid) into Kras(G12D)/Cre (KC) mice and Kras(G12D)/Trp53(R172H)/Cre (KPC) mice at 4 weeks of age (when pancreatic intraepithelial lesions are histologically evident). Antitumor humoral and cellular responses were analyzed by histology, immunohistochemistry, enzyme-linked immunosorbent assays, flow cytometry, and enzyme-linked immunosorbent spot and cytotoxicity assays. Survival was analyzed by Kaplan-Meier analysis. RESULTS: The ENO1 vaccine induced antibody and a cellular response and increased survival times by a median of 138 days in KC mice and 42 days in KPC mice compared with mice given the control vector. On histologic analysis, the vaccine appeared to slow tumor progression. The vaccinated mice had increased serum levels of anti-ENO1 immunoglobulin G, which bound the surface of carcinoma cells and induced complement-dependent cytotoxicity. ENO1 vaccination reduced numbers of myeloid-derived suppressor cells and T-regulatory cells and increased T-helper 1 and 17 responses. CONCLUSIONS: In a genetic model of pancreatic carcinoma, vaccination with ENO1 DNA elicits humoral and cellular immune responses against tumors, delays tumor progression, and significantly extends survival. This vaccination strategy might be developed as a neoadjuvant therapy for patients with PDA.
BACKGROUND & AIMS:Pancreatic ductal adenocarcinoma (PDA) is an aggressive tumor, and patients typically present with late-stage disease; rates of 5-year survival after pancreaticoduodenectomy are low. Antibodies against α-enolase (ENO1), a glycolytic enzyme, are detected in more than 60% of patients with PDA, and ENO1-specific T cells inhibit the growth of humanpancreatic xenograft tumors in mice. We investigated whether an ENO1 DNA vaccine elicits antitumor immune responses and prolongs survival of mice that spontaneously develop autochthonous, lethal pancreatic carcinomas. METHODS: We injected and electroporated a plasmid encoding ENO1 (or a control plasmid) into Kras(G12D)/Cre (KC) mice and Kras(G12D)/Trp53(R172H)/Cre (KPC) mice at 4 weeks of age (when pancreatic intraepithelial lesions are histologically evident). Antitumor humoral and cellular responses were analyzed by histology, immunohistochemistry, enzyme-linked immunosorbent assays, flow cytometry, and enzyme-linked immunosorbent spot and cytotoxicity assays. Survival was analyzed by Kaplan-Meier analysis. RESULTS: The ENO1 vaccine induced antibody and a cellular response and increased survival times by a median of 138 days in KC mice and 42 days in KPCmice compared with mice given the control vector. On histologic analysis, the vaccine appeared to slow tumor progression. The vaccinated mice had increased serum levels of anti-ENO1 immunoglobulin G, which bound the surface of carcinoma cells and induced complement-dependent cytotoxicity. ENO1 vaccination reduced numbers of myeloid-derived suppressor cells and T-regulatory cells and increased T-helper 1 and 17 responses. CONCLUSIONS: In a genetic model of pancreatic carcinoma, vaccination with ENO1 DNA elicits humoral and cellular immune responses against tumors, delays tumor progression, and significantly extends survival. This vaccination strategy might be developed as a neoadjuvant therapy for patients with PDA.
Authors: Julia Kravchenko; Emanuela Corsini; Marc A Williams; William Decker; Masoud H Manjili; Takemi Otsuki; Neetu Singh; Faha Al-Mulla; Rabeah Al-Temaimi; Amedeo Amedei; Anna Maria Colacci; Monica Vaccari; Chiara Mondello; A Ivana Scovassi; Jayadev Raju; Roslida A Hamid; Lorenzo Memeo; Stefano Forte; Rabindra Roy; Jordan Woodrick; Hosni K Salem; Elizabeth P Ryan; Dustin G Brown; William H Bisson; Leroy Lowe; H Kim Lyerly Journal: Carcinogenesis Date: 2015-05-22 Impact factor: 4.944
Authors: Gianluca Mucciolo; Claudia Curcio; Cecilia Roux; Wanda Y Li; Michela Capello; Roberta Curto; Roberto Chiarle; Daniele Giordano; Maria Antonietta Satolli; Rita Lawlor; Aldo Scarpa; Pavol Lukac; Dmitry Stakheev; Paolo Provero; Luca Vannucci; Tak W Mak; Francesco Novelli; Paola Cappello Journal: Proc Natl Acad Sci U S A Date: 2021-02-09 Impact factor: 11.205
Authors: Megan M Kaneda; Paola Cappello; Abraham V Nguyen; Natacha Ralainirina; Chanae R Hardamon; Philippe Foubert; Michael C Schmid; Ping Sun; Evangeline Mose; Michael Bouvet; Andrew M Lowy; Mark A Valasek; Roman Sasik; Francesco Novelli; Emilio Hirsch; Judith A Varner Journal: Cancer Discov Date: 2016-05-13 Impact factor: 39.397