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

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.

• Authors: 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, Yeong-Min Park
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 29 Pg. 27751-62 (Sep 29 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26336989 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adjuvants, Immunologic
• Cancer Vaccines
• Intercellular Signaling Peptides and Proteins
• Lectins
• NF-kappa B p50 Subunit
• NFKB1 protein, human
• Papillomavirus E7 Proteins
• Peptides
• TLR4 protein, human
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• ZG16B protein, human
• oncogene protein E7, Human papillomavirus type 16
• Nfkb1 protein, mouse

Topics

• Adenocarcinoma (metabolism)
• Adjuvants, Immunologic (chemistry)
• Animals
• CD8-Positive T-Lymphocytes (cytology)
• Cancer Vaccines (chemistry)
• Cell Line, Tumor
• Dendritic Cells (cytology, metabolism)
• Female
• Flow Cytometry
• Humans
• Immunologic Memory
• Intercellular Signaling Peptides and Proteins
• Lectins (biosynthesis, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Monocytes (cytology)
• NF-kappa B p50 Subunit (metabolism)
• Pancreatic Neoplasms (metabolism)
• Papillomavirus E7 Proteins (metabolism)
• Peptides (chemistry)
• Signal Transduction
• Toll-Like Receptor 4 (metabolism)
• Up-Regulation