Oncotarget

Research Papers:

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

Tae Heung Kang, Young Seob Kim, Seokho Kim, Benjamin Yang, Je-Jung Lee, Hyun-Ju Lee, Jaemin Lee, In Duk Jung, Hee Dong Han, Seung-Hyun Lee, Sang Seok Koh _, T.-C. Wu and Yeong-Min Park

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Oncotarget. 2015; 6:27751-27762. https://doi.org/10.18632/oncotarget.4859

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Abstract

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

Correspondence to:

Sang Seok Koh, e-mail: sskoh@dau.ac.kr

T.-C. Wu, e-mail: wutc@jhmi.edu

Yeong-Min Park, e-mail: immun3023@kku.ac.kr

Keywords: PAUF, dendritic cells, cancer vaccines, adjuvants, TLR4

Received: May 08, 2015     Accepted: July 27, 2015     Published: August 07, 2015

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.


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