Pancreatic adenocarcinoma upregulated factor serves as adjuvant by activating dendritic cells through stimulation of TLR4
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Tae Heung Kang1,*, Young Seob Kim1,*, Seokho Kim2,*, Benjamin Yang6, Je-Jung Lee3, Hyun-Ju Lee3, Jaemin Lee2, In Duk Jung1, Hee Dong Han1, Seung-Hyun Lee4, Sang Seok Koh5, T.-C. Wu6,7,8,9, Yeong-Min Park1
1Department of Immunology, KU Open Innovation Center, School of Medicine, Konkuk University, Chungju, South Korea
2Aging Research Institute, Korea Research Institute of Bioscience & Biotechnology, Daejeon, South Korea
3Research Center for Cancer Immunotherapy, Hwasun Hospital, Chonnam National University, Hwasun, Jeollanamdo, South Korea
4Department of Microbiology, KU Open Innovation Center, School of Medicine, Konkuk University, Chungju, South Korea
5Department of Biological Sciences, Dong-A University, Busan, South Korea
6Departments of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
7Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
8Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
9Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
*These authors have contributed equally to this work
Sang Seok Koh, e-mail: [email protected]
T.-C. Wu, e-mail: [email protected]
Yeong-Min Park, e-mail: [email protected]
Keywords: PAUF, dendritic cells, cancer vaccines, adjuvants, TLR4
Received: May 08, 2015 Accepted: July 27, 2015 Published: August 07, 2015
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.
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