The effect of alloferon on the enhancement of NK cell cytotoxicity against cancer via the up-regulation of perforin/granzyme B secretion

Seyeon Bae; Keunhee Oh; Hyemin Kim; Yejin Kim; Hang-Rae Kim; Young-Il Hwang; Dong-Sup Lee; Jae Seung Kang; Wang Jae Lee

doi:10.1016/j.imbio.2012.12.002

The effect of alloferon on the enhancement of NK cell cytotoxicity against cancer via the up-regulation of perforin/granzyme B secretion

Immunobiology. 2013 Aug;218(8):1026-33. doi: 10.1016/j.imbio.2012.12.002. Epub 2013 Jan 7.

Authors

Seyeon Bae¹, Keunhee Oh, Hyemin Kim, Yejin Kim, Hang-Rae Kim, Young-Il Hwang, Dong-Sup Lee, Jae Seung Kang, Wang Jae Lee

Affiliation

¹ Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.

PMID: 23434435
DOI: 10.1016/j.imbio.2012.12.002

Abstract

Alloferon is a novel immunomodulatory peptide originally isolated from infected insects. It has anti-viral and anti-tumor effects via the activation of NK cells. However, specific mechanisms leading to NK cell activation and anti-tumor responses yet to be clarified. In this study, we demonstrate that alloferon increases killing activity of NK cells to cancer cells via the up-regulation of the expression of NK-activating receptors, 2B4. In addition, the production of IFN-γ and TNF-α and granule exocytosis from NK cells against cancer cell were increased by alloferon. Lastly, the anti-tumor effect of alloferon was confirmed in vivo to demonstrate effective retardation of tumor growth in the human-to-mouse xenograft model. All taken together, these results suggest that alloferon has anti-tumor effects through up-regulation of NK-activating receptor 2B4 and the enhancement of granule exocytosis from NK cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, CD / biosynthesis*
Cell Line, Tumor
Cell Proliferation / drug effects
Colorectal Neoplasms / immunology
Cytotoxicity, Immunologic / drug effects
Cytotoxicity, Immunologic / immunology
Granzymes / metabolism*
Humans
Interferon-gamma / biosynthesis
Killer Cells, Natural / drug effects
Killer Cells, Natural / immunology*
Lymphocyte Activation / drug effects
Lymphocyte Activation / immunology
Male
Mice
Mice, Inbred BALB C
Mice, Inbred NOD
Mice, SCID
Neoplasm Transplantation
Peptides / pharmacology*
Perforin / metabolism*
Prostatic Neoplasms / immunology
Receptors, Immunologic / biosynthesis*
Signaling Lymphocytic Activation Molecule Family
Tumor Necrosis Factor-alpha / biosynthesis
Up-Regulation
Xenograft Model Antitumor Assays

Substances

Alloferon
Antigens, CD
CD244 protein, human
Peptides
Receptors, Immunologic
Signaling Lymphocytic Activation Molecule Family
Tumor Necrosis Factor-alpha
Perforin
Interferon-gamma
Granzymes