TNF-α and the IFN-γ-inducible protein 10 (IP-10/CXCL-10) delivered by parvoviral vectors act in synergy to induce antitumor effects in mouse glioblastoma

M. Enderlin, E. V. Kleinmann, S. Struyf, C. Buracchi, A. Vecchi, R. Kinscherf, F. Kiessling, S. Paschek, S. Sozzani, J. Rommelaere, J. J. Cornelis, J. Van Damme, C. Dinsart

Research output: Contribution to journalArticle

Abstract

Interferon-γ-inducible protein 10 is a potent chemoattractant for natural killer cells and activated T lymphocytes. It also displays angiostatic properties and some antitumor activity. Tumor necrosis factor-α (TNF-α) is a powerful immunomodulating cytokine with demonstrated tumoricidal activity in various tumor models and the ability to induce strong immune responses. This prompted us to evaluate the antitumor effects of recombinant parvoviruses designed to deliver IP-10 or TNF-α into a glioblastoma. When Gl261 murine glioma cells were infected in vitro with an IP-10- or TNF-α-transducing parvoviral vector and were subcutaneously implanted in mice, tumor growth was significantly delayed. Complete tumor regression was observed when the glioma cells were coinfected with both the vectors, demonstrating synergistic antitumor activity. In an established in vivo glioma model, however, repeated simultaneous peritumoral injection of the IP-10- and TNF-α-delivering parvoviruses failed to improve the therapeutic effect as compared with the use of a single cytokine-delivering vector. In this tumor model, cytokine-mediated immunostimulation, rather than inhibition of vascularization, is likely responsible for the therapeutic efficacy.

Original languageEnglish
Pages (from-to)149-160
Number of pages12
JournalCancer Gene Therapy
Volume16
Issue number2
DOIs
Publication statusPublished - Feb 2009

Fingerprint

Glioblastoma
Tumor Necrosis Factor-alpha
Glioma
Parvovirus
Cytokines
Neoplasms
Proteins
Chemokine CXCL10
Chemotactic Factors
Therapeutic Uses
Natural Killer Cells
Immunization
T-Lymphocytes
Injections
Growth
Therapeutics

Keywords

  • Cytokine
  • Glioma
  • IP-10/CXCL10
  • Parvoviral vector

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology

Cite this

TNF-α and the IFN-γ-inducible protein 10 (IP-10/CXCL-10) delivered by parvoviral vectors act in synergy to induce antitumor effects in mouse glioblastoma. / Enderlin, M.; Kleinmann, E. V.; Struyf, S.; Buracchi, C.; Vecchi, A.; Kinscherf, R.; Kiessling, F.; Paschek, S.; Sozzani, S.; Rommelaere, J.; Cornelis, J. J.; Van Damme, J.; Dinsart, C.

In: Cancer Gene Therapy, Vol. 16, No. 2, 02.2009, p. 149-160.

Research output: Contribution to journalArticle

Enderlin, M, Kleinmann, EV, Struyf, S, Buracchi, C, Vecchi, A, Kinscherf, R, Kiessling, F, Paschek, S, Sozzani, S, Rommelaere, J, Cornelis, JJ, Van Damme, J & Dinsart, C 2009, 'TNF-α and the IFN-γ-inducible protein 10 (IP-10/CXCL-10) delivered by parvoviral vectors act in synergy to induce antitumor effects in mouse glioblastoma', Cancer Gene Therapy, vol. 16, no. 2, pp. 149-160. https://doi.org/10.1038/cgt.2008.62
Enderlin, M. ; Kleinmann, E. V. ; Struyf, S. ; Buracchi, C. ; Vecchi, A. ; Kinscherf, R. ; Kiessling, F. ; Paschek, S. ; Sozzani, S. ; Rommelaere, J. ; Cornelis, J. J. ; Van Damme, J. ; Dinsart, C. / TNF-α and the IFN-γ-inducible protein 10 (IP-10/CXCL-10) delivered by parvoviral vectors act in synergy to induce antitumor effects in mouse glioblastoma. In: Cancer Gene Therapy. 2009 ; Vol. 16, No. 2. pp. 149-160.
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