nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.03.2013 | Original Paper

VP22 and cytosine deaminase fusion gene modified tissue-engineered neural stem cells for glioma therapy

verfasst von: Guishan Jin, Yiqiang Zhou, Qi Chai, Guidong Zhu, Fujian Xu, Fusheng Liu

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The herpes simplex virus type 1 tegument protein VP22 has the remarkable property of intercellular trafficking, thus making it a promising tool for improving gene transfer efficiency.

Methods

To investigate whether the fusion of VP22 to the cytosine deaminase (CD) suicide gene could enhance the therapeutic efficiency of neural stem cells (NSCs) in the treatment for C6 glioma, the lentiviral vectors pHIV-VP₂₂-EGFP, pHIV-CD, and pHIV-VP₂₂-CD were constructed based on the pHIV-EGFP vector. After packaging, vectors were transduced into rat NSCs.

Results

Fluorescence-activated cell sorting analysis revealed that the fusion of VP22-EGFP increased the expression rate of EGFP in NSCs compared with lenti-EGFP transduced cells. Under incubation with the prodrug 5-fluorocytosine (5-FC), the survival rates of C6 cells co-cultured with NSCs/VP₂₂-CD (NSCs transduced with lenti-VP₂₂-CD) decreased tremendously compared with those of C6 and NSCs/CD. Similar results were also observed in vivo; a significant reduction in tumor volumes in C6 glioma-bearing rats was observed in the NSCs/VP₂₂-CD therapy group when compared with other control groups.

Conclusions

Our results reveal that VP22 increases the transduction efficiency of lentivirus into NSCs and enhances the therapeutic efficacy of CD-engineered rat NSCs in the treatment for C6 glioma, demonstrating that VP22 might be a useful tool for the gene therapy of engineered NSCs and providing a potential novel strategy for enhancing the effectiveness of gene therapy in other diseases.

Aboody KS, Najbauer J, Danks MK (2008) Stem and progenitor cell-mediated tumor selective gene therapy. Gene Ther 15:739–752PubMedCrossRef

Ahmed AU, Lesniak MS (2011) Glioblastoma multiforme: can neural stem cells deliver the therapeutic payload and fulfill the clinical promise? Expert Rev Neurother 11:775–777PubMedCrossRef

Barresi V, Belluardo N, Sipione S, Mudo G, Cattaneo E, Condorelli DF (2003) Transplantation of prodrug-converting neural progenitor cells for brain tumor therapy. Cancer Gene Ther 10:396–402PubMedCrossRef

Benedetti S, Pirola B, Pollo B, Magrassi L, Bruzzone MG, Rigamonti D, Galli R, Selleri S, Di Meco F, De Fraja C, Vescovi A, Cattaneo E, Finocchiaro G (2000) Gene therapy of experimental brain tumors using neural progenitor cells. Nat Med 6:447–450PubMedCrossRef

Binello E, Germano IM (2012) Stem cells as therapeutic vehicles for the treatment of high-grade gliomas. Neuro Oncol 14:256–265PubMedCrossRef

Elliott G, O’Hare P (1997) Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell 88:223–233PubMedCrossRef

Freeman SM, Abboud CN, Whartenby KA, Packman CH, Koeplin DS, Moolten FL, Abraham GN (1993) The “bystander effect”: tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res 53:5274–5283PubMed

Glass R, Synowitz M, Kronenberg G, Walzlein JH, Markovic DS, Wang LP, Gast D, Kiwit J, Kempermann G, Kettenmann H (2005) Glioblastoma-induced attraction of endogenous neural precursor cells is associated with improved survival. J Neurosci 25:2637–2646PubMedCrossRef

Huber BE, Austin EA, Richards CA, Davis ST, Good SS (1994) Metabolism of 5-fluorocytosine to 5-fluorouracil in human colorectal tumor cells transduced with the cytosine deaminase gene: significant antitumor effects when only a small percentage of tumor cells express cytosine deaminase. Proc Natl Acad Sci USA 91:8302–8306PubMedCrossRef

Jin GS, Liu FS, Chai Q, Wang JJ, Li JH (2008) Stable EGFP gene expression in C6 glioma cell line after transduction with HIV-1-based lentiviral vector. Chin J Cancer Res 20:243–248CrossRef

Kretz A, Wybranietz WA, Hermening S, Lauer UM, Isenmann S (2003) HSV-1 VP22 augments adenoviral gene transfer to CNS neurons in the retina and striatum in vivo. Mol Ther 7:659–669PubMedCrossRef

Lai Z, Han I, Zirzow G, Brady RO, Reiser J (2000) Intercellular delivery of a herpes simplex virus VP22 fusion protein from cells infected with lentiviral vectors. Proc Natl Acad Sci USA 97:11297–11302PubMedCrossRef

Lee KC, Hamstra DA, Bullarayasamudram S, Bhojani MS, Moffat BA, Dornfeld KJ, Ross BD, Rehemtulla A (2006) Fusion of the HSV-1 tegument protein vp22 to cytosine deaminase confers enhanced bystander effect and increased therapeutic benefit. Gene Ther 13:127–137PubMedCrossRef

Lefranc F, Brotchi J, Kiss R (2005) Possible future issues in the treatment of glioblastomas: special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis. J Clin Oncol 23:2411–2422PubMedCrossRef

Liu CS, Kong B, Xia HH, Ellem KA, Wei MQ (2001) VP22 enhanced intercellular trafficking of HSV thymidine kinase reduced the level of ganciclovir needed to cause suicide cell death. J Gene Med 3:145–152PubMedCrossRef

Lobanov VA, Zheng C, Babiuk LA, van Drunen LDHS (2010) Intracellular trafficking of VP22 in bovine herpesvirus-1 infected cells. Virology 396:189–202PubMedCrossRef

Naito S, von Eschenbach AC, Giavazzi R, Fidler IJ (1986) Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Res 46:4109–4115PubMed

Oh MC, Lim DA (2009) Novel treatment strategies for malignant gliomas using neural stem cells. Neurotherapeutics 6:458–464PubMedCrossRef

Phelan A, Elliott G, O’Hare P (1998) Intercellular delivery of functional p53 by the herpesvirus protein VP22. Nat Biotechnol 16:440–443PubMedCrossRef

Ricard D, Idbaih A, Ducray F, Lahutte M, Hoang-Xuan K, Delattre JY (2012) Primary brain tumours in adults. Lancet 379:1984–1996PubMedCrossRef

Sathornsumetee S, Rich JN (2008) Designer therapies for glioblastoma multiforme. Ann NY Acad Sci 1142:108–132PubMedCrossRef

Tabatabai G, Wick W, Weller M (2011) Stem cell-mediated gene therapies for malignant gliomas: a promising targeted therapeutic approach? Discov Med 11:529–536PubMed

Tanaka M, Kato A, Satoh Y, Ide T, Sagou K, Kimura K, Hasegawa H, Kawaguchi Y (2012) Herpes simplex virus 1 VP22 regulates translocation of multiple viral and cellular proteins and promotes neurovirulence. J Virol 86:5264–5277PubMedCrossRef

Thaci B, Ahmed AU, Ulasov IV, Tobias AL, Han Y, Aboody KS, Lesniak MS (2012) Pharmacokinetic study of neural stem cell-based cell carrier for oncolytic virotherapy: targeted delivery of the therapeutic payload in an orthotopic brain tumor model. Cancer Gene Ther 19:431–442PubMedCrossRef

Ubiali F, Nava S, Nessi V, Frigerio S, Parati E, Bernasconi P, Mantegazza R, Baggi F (2007) Allorecognition of human neural stem cells by peripheral blood lymphocytes despite low expression of MHC molecules: role of TGF-beta in modulating proliferation. Int Immunol 19:1063–1074PubMedCrossRef

Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507PubMedCrossRef

Wybranietz WA, Prinz F, Spiegel M, Schenk A, Bitzer M, Gregor M, Lauer UM (1999) Quantification of VP22-GFP spread by direct fluorescence in 15 commonly used cell lines. J Gene Med 1:265–274PubMedCrossRef

Yazawa K, Fisher WE, Brunicardi FC (2002) Current progress in suicide gene therapy for cancer. World J Surg 26:783–789PubMedCrossRef

Yuan X, Hu J, Belladonna ML, Black KL, Yu JS (2006) Interleukin-23-expressing bone marrow-derived neural stem-like cells exhibit antitumor activity against intracranial glioma. Cancer Res 66:2630–2638PubMedCrossRef

Zavaglia D, Favrot MC, Eymin B, Tenaud C, Coll JL (2003) Intercellular trafficking and enhanced in vivo antitumour activity of a non-virally delivered P27-VP22 fusion protein. Gene Ther 10:314–325PubMedCrossRef

Titel: VP22 and cytosine deaminase fusion gene modified tissue-engineered neural stem cells for glioma therapy
verfasst von: Guishan Jin
Yiqiang Zhou
Qi Chai
Guidong Zhu
Fujian Xu
Fusheng Liu
Publikationsdatum: 01.03.2013
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 3/2013
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-012-1347-3

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

VP22 and cytosine deaminase fusion gene modified tissue-engineered neural stem cells for glioma therapy

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Onkologie

Alter verschlechtert Prognose bei Endometriumkarzinom

Darf man die Behandlung eines Neonazis ablehnen?

Erhöhte Mortalität bei postpartalem Brustkrebs

Hypertherme Chemotherapie bietet Chance auf Blasenerhalt

Update Onkologie

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2013

Brain metastases as the first symptom of lung cancer: a clinical study from an Asian medical center

Role of pharmacogenetics on adjuvant chemotherapy-induced neutropenia in Chinese breast cancer patients

Phase I/II study of the tumour-targeting human monoclonal antibody–cytokine fusion protein L19-TNF in patients with advanced solid tumours

PPP1R13L variant associated with prognosis for patients with rectal cancer

Direct progression of capsular invasive carcinomas from subcapsular focal hyperplasias induced by hypothyroidism-mediated tumor promotion in a rat two-stage thyroid carcinogenesis model

Predictive factors of [18F]-Choline PET/CT in 170 patients with increasing PSA after primary radical treatment

Neu im Fachgebiet Onkologie

Alter verschlechtert Prognose bei Endometriumkarzinom

Darf man die Behandlung eines Neonazis ablehnen?

Erhöhte Mortalität bei postpartalem Brustkrebs

Hypertherme Chemotherapie bietet Chance auf Blasenerhalt

Update Onkologie