NDLI: Antiangiogenic tumor therapy by DNA vaccine inducing aquaporin-1-specific CTL based on ubiquitin-proteasome system in mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ishii, Kazunari Chou, Bin Tanaka, Keiji Duan, Xuefeng Okano, Shinji Sakai, Tohru Himeno, Kunisuke Hiromatsu, Kenji Murata, Shigeo
Description	Country affiliation: Japan Author Affiliation: Chou B ( Department of Microbiology and Immunology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.)
Abstract	Aquaporin-1 (AQP-1) is a water channel protein highly expressed in the vascular endothelial cells of proliferating tissues including malignant cancers. Given that in APC ubiquitinated peptides are effectively introduced into proteasomes from which CD8 epitopes are excised, we fused ubiquitin with AQP-1 (pUB-AQP-1) to produce a DNA vaccine. In C57BL/6J mice immunized with pUB-AQP-1, the growth of B16F10 melanoma was profoundly inhibited. The antitumor effect of the pUB-AQP-1 DNA vaccine was largely mediated by CD8 T cells, which secrete IFN-Î³, perforin, and granzyme-B in the presence of APCs transfected with pUB-AQP-1. AQP-1-specific CD8 T cells possessed cytotoxic activity both in vivo and in vitro. After tumor challenge, the microvessel density decreased and the ratio of total blood vessel area to tumor area was significantly reduced as compared with control mice, resulting in a dramatic suppression of tumor growth. The immunization effect was completely abrogated in immunoproteasome-deficient mice. Strikingly this pUB-AQP-1 DNA vaccine was also effective against Colon 26 colon tumors (BALB/c) and MBT/2 bladder tumors (C3H/HeN). Thus, this ubiquitin-conjugated DNA immunization-targeting tumor vasculature is a valid and promising antitumor therapy. This vaccine works across the barriers of tumor species and MHC class I differences in host mice.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Aquaporin 1 Immunology Cancer Vaccines Pharmacology Neoplasms, Experimental Therapy T-lymphocytes, Cytotoxic Vaccines, Dna Animals Blotting, Western Immunohistochemistry Mice Mice, Inbred Balb C Mice, Inbred C3h Mice, Inbred C57bl Blood Supply Neovascularization, Pathologic Proteasome Endopeptidase Complex Reverse Transcriptase Polymerase Chain Reaction Transfection Ubiquitin Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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