A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model

A therapeutic vaccine against minimal residual cancer cells is needed for the treatment of patients with colorectal cancer. Several gene therapy studies have revealed that the combination of a suicide gene and cytokine gene might induce effective antitumor immunity. In this study, we constructed an...

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Main Authors:	HIGASHI, KOSUKE, HAZAMA, SHOICHI, ARAKI, ATSUHIRO, YOSHIMURA, KIYOSHI, IIZUKA, NORIO, YOSHINO, SHIGEFUMI, NOMA, TAKAFUMI, OKA, MASAKI
Format:	Online
Language:	English
Published:	D.A. Spandidos 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151806/

id	pubmed-4151806
recordtype	oai_dc
spelling	pubmed-41518062014-09-03 A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model HIGASHI, KOSUKE HAZAMA, SHOICHI ARAKI, ATSUHIRO YOSHIMURA, KIYOSHI IIZUKA, NORIO YOSHINO, SHIGEFUMI NOMA, TAKAFUMI OKA, MASAKI Articles A therapeutic vaccine against minimal residual cancer cells is needed for the treatment of patients with colorectal cancer. Several gene therapy studies have revealed that the combination of a suicide gene and cytokine gene might induce effective antitumor immunity. In this study, we constructed an interleukin (IL)-18 and herpes simplex virus-thymidine kinase (HSV-TK) expression vector driven by the human telomerase reverse transcriptase (hTERT) promoter to study the efficacy of combination gene therapy with IL-18 and the HSV-TK suicide gene. Low immunogenic colon 26 cells were used for transfection and inoculation into syngeneic BALB/c mice. Large established tumors of colon 26 transfectants expressing IL-18 and HSV-TK driven by the hTERT promoter were completely eradicated after GCV administration in syngeneic BALB/c mice. Immunohistochemical analysis at the tumor rejection sites revealed enormous infiltrations of CD8+ T lymphocytes as well as CD4+ T lymphocytes and CD11b+ monocytes. Moreover, established distant tumors were completely eradicated by vaccination with the IL-18 and HSV-TK transfectants in combination with GCV. These data suggest that the IL-18 and suicide gene therapy can elicit antitumor specific immunity. In conclusion, gene therapy with IL-18 and HSV-TK plasmid vector driven by the hTERT promoter may be useful for cancer vaccination. D.A. Spandidos 2014-07-22 /pmc/articles/PMC4151806/ /pubmed/25051201 http://dx.doi.org/10.3892/ijo.2014.2557 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	HIGASHI, KOSUKE HAZAMA, SHOICHI ARAKI, ATSUHIRO YOSHIMURA, KIYOSHI IIZUKA, NORIO YOSHINO, SHIGEFUMI NOMA, TAKAFUMI OKA, MASAKI
spellingShingle	HIGASHI, KOSUKE HAZAMA, SHOICHI ARAKI, ATSUHIRO YOSHIMURA, KIYOSHI IIZUKA, NORIO YOSHINO, SHIGEFUMI NOMA, TAKAFUMI OKA, MASAKI A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model
author_facet	HIGASHI, KOSUKE HAZAMA, SHOICHI ARAKI, ATSUHIRO YOSHIMURA, KIYOSHI IIZUKA, NORIO YOSHINO, SHIGEFUMI NOMA, TAKAFUMI OKA, MASAKI
author_sort	HIGASHI, KOSUKE
title	A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model
title_short	A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model
title_full	A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model
title_fullStr	A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model
title_full_unstemmed	A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model
title_sort	novel cancer vaccine strategy with combined il-18 and hsv-tk gene therapy driven by the htert promoter in a murine colorectal cancer model
description	A therapeutic vaccine against minimal residual cancer cells is needed for the treatment of patients with colorectal cancer. Several gene therapy studies have revealed that the combination of a suicide gene and cytokine gene might induce effective antitumor immunity. In this study, we constructed an interleukin (IL)-18 and herpes simplex virus-thymidine kinase (HSV-TK) expression vector driven by the human telomerase reverse transcriptase (hTERT) promoter to study the efficacy of combination gene therapy with IL-18 and the HSV-TK suicide gene. Low immunogenic colon 26 cells were used for transfection and inoculation into syngeneic BALB/c mice. Large established tumors of colon 26 transfectants expressing IL-18 and HSV-TK driven by the hTERT promoter were completely eradicated after GCV administration in syngeneic BALB/c mice. Immunohistochemical analysis at the tumor rejection sites revealed enormous infiltrations of CD8+ T lymphocytes as well as CD4+ T lymphocytes and CD11b+ monocytes. Moreover, established distant tumors were completely eradicated by vaccination with the IL-18 and HSV-TK transfectants in combination with GCV. These data suggest that the IL-18 and suicide gene therapy can elicit antitumor specific immunity. In conclusion, gene therapy with IL-18 and HSV-TK plasmid vector driven by the hTERT promoter may be useful for cancer vaccination.
publisher	D.A. Spandidos
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151806/
_version_	1613130123577393152

A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model

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