A candidate for cancer gene therapy: MIP-1α gene transfer to an adenocarcinoma cell line reduced tumorigenicity and induced protective immunity in immunocompetent mice

Emi Nakashima, Akiko Oya, Yuri Kubota, Naomi Kanada, Ryo Matsushita, Kazuyoshi Takeda, Fujio Ichimura, Kouji Kuno, Naofumi Mukaida, Kunitaka Hirose, Isao Nakanishi, Toshimitsu Ujiie, Kouji Matsushima

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Abstract

Purpose. The evaluate the possibility of cancer gene therapy by the gene delivery of chemokine, the effects of human macrophage inflammatory protein 1α (hu-MIP-1α), murine-macrophage inflammatory protein 1α (mu-MIP-1α), and human-interleukin 8 (hu-IL-8) on tumor progression and immunization were studied. Methods. Cachexia-inducing and highly tumorigenic adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid, hu-MIP-1α, mu-MIP-1α, or hu-IL-8 expression vector. The production of hu-MIP-1α reached > 1.5 ng/ml in vitro when transfectant cells were cultured at a cell density of 2 x 10 5 cells in 7 ml for 3 days. Immunocompetent BALB/c mice were inoculated into the footpad with the tumor cells, and then primary tumor growth, morphological analyses, and tumor immunogenicity were studied. Results. The secretion of hu-MIP-1α, mu-MIP-1α, and hu-IL-8 did not affect the growth rate in vitro. Reduced tumorigenicities in vivo were observed in transfected cells with hu-MTP-1α and mu-MIP-1α. Morphologic observation of the site of inoculation of cells transfected with hu-MIP-1α showed infiltration of macrophages and neutrophils on the 5th day after the inoculation. Mice that had rejected cells transfected with hu-MIP-1α gene were immune to a subsequent challenge with the parental cells. Conclusions. The rejection of the cells depends on cytolysis and generates potent and long lasting antitumor immunity. These data suggest that tumor cells transfected with the MIP-1α gene might be useful as an effective therapy for the treatment of certain tumors.

Original languageEnglish
Pages (from-to)1896-1901
Number of pages6
JournalPharmaceutical Research
Volume13
Issue number12
DOIs
Publication statusPublished - 1996
Externally publishedYes

Fingerprint

Gene transfer
Macrophage Inflammatory Proteins
Gene therapy
Neoplasm Genes
Genetic Therapy
Immunity
Adenocarcinoma
Cells
Cell Line
Tumors
Genes
Interleukin-8
Neoplasms
Immunization
Cachexia
Neutrophil Infiltration
Macrophages
Growth
Chemokines
Infiltration

Keywords

  • Chemokine
  • Gene transfer
  • MIP-1α
  • Protective immunity

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

A candidate for cancer gene therapy : MIP-1α gene transfer to an adenocarcinoma cell line reduced tumorigenicity and induced protective immunity in immunocompetent mice. / Nakashima, Emi; Oya, Akiko; Kubota, Yuri; Kanada, Naomi; Matsushita, Ryo; Takeda, Kazuyoshi; Ichimura, Fujio; Kuno, Kouji; Mukaida, Naofumi; Hirose, Kunitaka; Nakanishi, Isao; Ujiie, Toshimitsu; Matsushima, Kouji.

In: Pharmaceutical Research, Vol. 13, No. 12, 1996, p. 1896-1901.

Research output: Contribution to journalArticle

Nakashima, E, Oya, A, Kubota, Y, Kanada, N, Matsushita, R, Takeda, K, Ichimura, F, Kuno, K, Mukaida, N, Hirose, K, Nakanishi, I, Ujiie, T & Matsushima, K 1996, 'A candidate for cancer gene therapy: MIP-1α gene transfer to an adenocarcinoma cell line reduced tumorigenicity and induced protective immunity in immunocompetent mice', Pharmaceutical Research, vol. 13, no. 12, pp. 1896-1901. https://doi.org/10.1023/A:1016057830271
Nakashima, Emi ; Oya, Akiko ; Kubota, Yuri ; Kanada, Naomi ; Matsushita, Ryo ; Takeda, Kazuyoshi ; Ichimura, Fujio ; Kuno, Kouji ; Mukaida, Naofumi ; Hirose, Kunitaka ; Nakanishi, Isao ; Ujiie, Toshimitsu ; Matsushima, Kouji. / A candidate for cancer gene therapy : MIP-1α gene transfer to an adenocarcinoma cell line reduced tumorigenicity and induced protective immunity in immunocompetent mice. In: Pharmaceutical Research. 1996 ; Vol. 13, No. 12. pp. 1896-1901.
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T1 - A candidate for cancer gene therapy

T2 - MIP-1α gene transfer to an adenocarcinoma cell line reduced tumorigenicity and induced protective immunity in immunocompetent mice

AU - Nakashima, Emi

AU - Oya, Akiko

AU - Kubota, Yuri

AU - Kanada, Naomi

AU - Matsushita, Ryo

AU - Takeda, Kazuyoshi

AU - Ichimura, Fujio

AU - Kuno, Kouji

AU - Mukaida, Naofumi

AU - Hirose, Kunitaka

AU - Nakanishi, Isao

AU - Ujiie, Toshimitsu

AU - Matsushima, Kouji

PY - 1996

Y1 - 1996

N2 - Purpose. The evaluate the possibility of cancer gene therapy by the gene delivery of chemokine, the effects of human macrophage inflammatory protein 1α (hu-MIP-1α), murine-macrophage inflammatory protein 1α (mu-MIP-1α), and human-interleukin 8 (hu-IL-8) on tumor progression and immunization were studied. Methods. Cachexia-inducing and highly tumorigenic adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid, hu-MIP-1α, mu-MIP-1α, or hu-IL-8 expression vector. The production of hu-MIP-1α reached > 1.5 ng/ml in vitro when transfectant cells were cultured at a cell density of 2 x 10 5 cells in 7 ml for 3 days. Immunocompetent BALB/c mice were inoculated into the footpad with the tumor cells, and then primary tumor growth, morphological analyses, and tumor immunogenicity were studied. Results. The secretion of hu-MIP-1α, mu-MIP-1α, and hu-IL-8 did not affect the growth rate in vitro. Reduced tumorigenicities in vivo were observed in transfected cells with hu-MTP-1α and mu-MIP-1α. Morphologic observation of the site of inoculation of cells transfected with hu-MIP-1α showed infiltration of macrophages and neutrophils on the 5th day after the inoculation. Mice that had rejected cells transfected with hu-MIP-1α gene were immune to a subsequent challenge with the parental cells. Conclusions. The rejection of the cells depends on cytolysis and generates potent and long lasting antitumor immunity. These data suggest that tumor cells transfected with the MIP-1α gene might be useful as an effective therapy for the treatment of certain tumors.

AB - Purpose. The evaluate the possibility of cancer gene therapy by the gene delivery of chemokine, the effects of human macrophage inflammatory protein 1α (hu-MIP-1α), murine-macrophage inflammatory protein 1α (mu-MIP-1α), and human-interleukin 8 (hu-IL-8) on tumor progression and immunization were studied. Methods. Cachexia-inducing and highly tumorigenic adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid, hu-MIP-1α, mu-MIP-1α, or hu-IL-8 expression vector. The production of hu-MIP-1α reached > 1.5 ng/ml in vitro when transfectant cells were cultured at a cell density of 2 x 10 5 cells in 7 ml for 3 days. Immunocompetent BALB/c mice were inoculated into the footpad with the tumor cells, and then primary tumor growth, morphological analyses, and tumor immunogenicity were studied. Results. The secretion of hu-MIP-1α, mu-MIP-1α, and hu-IL-8 did not affect the growth rate in vitro. Reduced tumorigenicities in vivo were observed in transfected cells with hu-MTP-1α and mu-MIP-1α. Morphologic observation of the site of inoculation of cells transfected with hu-MIP-1α showed infiltration of macrophages and neutrophils on the 5th day after the inoculation. Mice that had rejected cells transfected with hu-MIP-1α gene were immune to a subsequent challenge with the parental cells. Conclusions. The rejection of the cells depends on cytolysis and generates potent and long lasting antitumor immunity. These data suggest that tumor cells transfected with the MIP-1α gene might be useful as an effective therapy for the treatment of certain tumors.

KW - Chemokine

KW - Gene transfer

KW - MIP-1α

KW - Protective immunity

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