Semliki Forest virus‐mediated gene therapy of the RG2 rat glioma

作者: F. P. Roche , B. J. Sheahan , S. M. O'Mara , G. J. Atkins

DOI: 10.1111/J.1365-2990.2010.01110.X

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摘要: F. P. Roche, B. J. Sheahan, S. M. O'Mara and G. Atkins (2010) Neuropathology Applied Neurobiology36, 648–660 Semliki Forest virus-mediated gene therapy of the RG2 rat glioma Aims: Glioblastoma multiforme is most common malignant adult brain tumour. Despite numerous advances in cancer there has been little change prognosis glioblastoma multiforme, which remains invariably fatal. We examined virus virus-like particle (SFV VLP) expression system encoding interleukin-12 (IL-12) as a therapeutic intervention against syngeneic glioma model. Methods: Glioma-bearing rats were treated with IL-12-encoding SFV VLPs via an implanted cannula. Animals 5 × 107 (low-dose) or 5 × 108 (high-dose) per treatment effect on growth survival was assessed. Results: Low-dose produced 70% reduction tumour volume, associated significant extension (20.45%) that dependent upon IL-12 expression. High-dose resulted 87% related to oncolytic capacity VLP system. delivery central nervous (CNS) demonstrated potential vector induce lethal pathology unrelated replication-competent high-level Treatment-related death pronounced high dose-treated animals appeared be result inflammation, necrosis oedema at inoculation site. Conclusion: The efficacy approach for model addition this, broad tropism SFV-based may limit use CNS unless this inherent limitation can overcome.

参考文章(35)
Johanna E. Portielje, Jan Gratama, Heidi H. van Ojik, Gerrit Stoter, Wim H. Kruit, IL-12: a promising adjuvant for cancer vaccination. Cancer Immunology, Immunotherapy. ,vol. 52, pp. 133- 144 ,(2003) , 10.1007/S00262-002-0356-5
Mark A. Kay, Joseph C Glorioso, Luigi Naldini, Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics Nature Medicine. ,vol. 7, pp. 33- 40 ,(2001) , 10.1038/83324
Charles G. Orosz, Steven M. James, Rolf F. Barth, Jone-Jiun Tzeng, Phenotype and functional activity of tumor-infiltrating lymphocytes isolated from immunogenic and nonimmunogenic rat brain tumors. Cancer Research. ,vol. 51, pp. 2373- 2378 ,(1991)
Finbarr J. Murphy, Mark P. Hayes, Parris R. Burd, Disparate Intracellular Processing of Human IL-12 Preprotein Subunits: Atypical Processing of the P35 Signal Peptide The Journal of Immunology. ,vol. 164, pp. 839- 847 ,(2000) , 10.4049/JIMMUNOL.164.2.839
Pieter Wesseling, Dirk J. Ruiter, and Peter C. Burger, Angiogenesis in brain tumors: pathobiological and clinical aspects Journal of Neuro-oncology. ,vol. 32, pp. 253- 265 ,(1997) , 10.1023/A:1005746320099
H Tahara, H D Edington, M J Brunda, S F Wolf, R D Schreiber, W J Storkus, M K Gately, M A Nalesnik, T G McKinney, C L Nastala, Recombinant IL-12 administration induces tumor regression in association with IFN-gamma production. Journal of Immunology. ,vol. 153, pp. 1697- 1706 ,(1994)
Robert L. Martuza, Samuel D. Rabkin, Hidefumi Kojima, Masahiro Toda, In Situ Cancer Vaccination: An IL-12 Defective Vector/Replication-Competent Herpes Simplex Virus Combination Induces Local and Systemic Antitumor Activity Journal of Immunology. ,vol. 160, pp. 4457- 4464 ,(1998)
Mark J. Smyth, Masaru Taniguchi, Shayna E. A. Street, The Anti-Tumor Activity of IL-12: Mechanisms of Innate Immunity That Are Model and Dose Dependent Journal of Immunology. ,vol. 165, pp. 2665- 2670 ,(2000) , 10.4049/JIMMUNOL.165.5.2665
Sonia Minuzzo, Lidia Moserle, Stefano Indraccolo, Alberto Amadori, Angiogenesis meets immunology: Cytokine gene therapy of cancer Molecular Aspects of Medicine. ,vol. 28, pp. 59- 86 ,(2007) , 10.1016/J.MAM.2006.12.008