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Oncotarget. 2015 Sep 29;6(29):27751-62. doi: 10.18632/oncotarget.4859.

Pancreatic adenocarcinoma upregulated factor serves as adjuvant by activating dendritic cells through stimulation of TLR4.

Author information

1
Department of Immunology, KU Open Innovation Center, School of Medicine, Konkuk University, Chungju, South Korea.
2
Aging Research Institute, Korea Research Institute of Bioscience & Biotechnology, Daejeon, South Korea.
3
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
4
Research Center for Cancer Immunotherapy, Hwasun Hospital, Chonnam National University, Hwasun, Jeollanamdo, South Korea.
5
Department of Microbiology, KU Open Innovation Center, School of Medicine, Konkuk University, Chungju, South Korea.
6
Department of Biological Sciences, Dong-A University, Busan, South Korea.
7
Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
8
Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
9
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.

Abstract

Dendritic cell (DC) based cancer vaccines represent a promising immunotherapeutic strategy against cancer. To enhance the modest immunogenicity of DC vaccines, various adjuvants are often incorporated. Particularly, most of the common adjuvants are derived from bacteria. In the current study, we evaluate the use of a human pancreatic cancer derived protein, pancreatic adenocarcinoma upregulated factor (PAUF), as a novel DC vaccine adjuvant. We show that PAUF can induce activation and maturation of DCs and activate NFkB by stimulating the Toll-like receptor signaling pathway. Furthermore, vaccination with PAUF treated DCs pulsed with E7 or OVA peptides leads to generation of E7 or OVA-specific CD8+ T cells and memory T cells, which correlate with long term tumor protection and antitumor effects against TC-1 and EG.7 tumors in mice. Finally, we demonstrated that PAUF mediated DC activation and immune stimulation are dependent on TLR4. Our data provides evidence supporting PAUF as a promising adjuvant for DC based therapies, which can be applied in conjunction with other cancer therapies. Most importantly, our results serve as a reference for future investigation of human based adjuvants.

KEYWORDS:

PAUF; TLR4; adjuvants; cancer vaccines; dendritic cells

PMID:
26336989
PMCID:
PMC4695023
DOI:
10.18632/oncotarget.4859
[Indexed for MEDLINE]
Free PMC Article

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