Gene Therapy for Malignant Glioma Patients

Puumalainen, Anu-Maaria; Vapalahti, Matti; Ylä‐Herttuala, Seppo

doi:10.1007/978-1-4615-5357-1_78

Cited by 13 publications

(5 citation statements)

References 9 publications

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“…Several studies have concluded that gene transfer to solid tumors is a limiting factor in gene therapy. [36][37][38][39][40] Enger et al 41 have shown that tumor spheroids infected with rAAV-lacZ efficiently penetrated and transduced within the central regions as compared to spheroids infected with an adenovirus carrying the lacZ gene. These observations were consistently observed in spheroids from different tumors and with increasing concentration of viral particles.…”

mentioning

confidence: 99%

Recombinant adeno‐associated virus (rAAV) expressing TFPI‐2 inhibits invasion, angiogenesis and tumor growth in a human glioblastoma cell line

Yanamandra

Kondraganti

Gondi

et al. 2005

Intl Journal of Cancer

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Recombinant adeno-associated viruses (rAAV) have become the vector of choice for many gene therapy protocols. rAAVs have a number of attractive features including long-term transgene expression and the ability to transduce both dividing and nondividing cells. We have shown previously the anti-cancer role of tissue factor pathway inhibitor-2 (TFPI-2), a matrix-associated serine protease inhibitor, in human glioblastomas. As a result of our present study, in which 0.8-kb fragment of human TFPI-2 was cloned into the adeno-associated viral vectors (rAAA-TFPI-2), rAAV-TFPI-2 infection of SNB19 cells significantly increased TFPI-2 as determined by Western blotting. As assessed by spheroid and Matrigel assays, infection of SNB19 cells with rAAV-TFPI-2 significantly reduced migration and invasion in a dosedependent manner. Tumor spheroids infected with rAAV-TFPI-2 and co-cultured with fetal rat brain aggregates did not invade rat brain aggregates, whereas 90-95% of the mock and AAV-CMV infected cells invaded rat brain aggregates. In vitro angiogenesis studies (tumor cells co-cultured with endothelial cells or endothelial cells seeded on matrigel) showed reduction of capillary-like structure formation in rAAV-TFPI-2-treated cells as compared to parental and mock-transfected cells. In in vivo angiogenesis results demonstrated the formation of microvessels in SNB19 parental cells and this formation was inhibited when the SNB19 cells were infected with rAAV-TFPI-2. Further, we observed a large reduction of tumor growth in SNB19 cells treated with rAAV-TFPI-2 virus injected intracerebrally when compared to controls. Our study demonstrates that rAAV-TFPI-2-mediated gene therapy offers a novel tool for the treatment of brain tumors. ' 2005 Wiley-Liss, Inc.

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confidence: 99%

Recombinant adeno‐associated virus (rAAV) expressing TFPI‐2 inhibits invasion, angiogenesis and tumor growth in a human glioblastoma cell line

Yanamandra

Kondraganti

Gondi

et al. 2005

Intl Journal of Cancer

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“…Nonreplicating viruses are used to deliver toxic or therapeutic genes. Such viral vectors have so far been only partially effective because only a small percentage of tumor cells are infected (Puumalainen et al, 1998;Rainov and Ren, 2003). An alternate strategy is the use of replicating viruses that target, infect, produce progeny virus to infect more tumor cells, and kill infected cells.…”

Section: Introductionmentioning

confidence: 99%

Systemic Vesicular Stomatitis Virus Selectively Destroys Multifocal Glioma and Metastatic Carcinoma in Brain

Özduman¹,

Wollmann²,

Piepmeier³

et al. 2008

J. Neurosci.

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“…On the other hand, a prospective randomized Phase III clinical study of retroviral (RV) gene therapy in primary malignant glioma failed to demonstrate significant extension of the progression-free or overall survival times in RV-treated patients. [86] The failure of this RV gene therapy study may be due to the low tumor cell transduction rate observed in vivo. Biological effects of the treatment may heavily depend on the choice of transgene/prodrug system and on the vector delivery methods.…”

Section: Clinical Trialsmentioning

confidence: 99%

Genetic therapy in gliomas: Historical analysis and future perspectives

Mattei¹,

Ramina²,

Miura³

et al. 2005

Neurol India

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High-grade gliomas are relatively frequent in adults, and consist of the most malignant kind of primary brain tumor. Being resistant to standard treatment modalities such as surgery, radiation, and chemotherapy, it is fatal within 1 to 2 years of onset of symptoms. Although several gene therapy systems proved to be efficient in controlling or eradicating these tumors in animal models, the clinical studies performed so far were not equally successful. Most clinical studies showed that methodologies that increase tumor infection/transduction and, consequently confer more permanent activity against the tumor, will lead to enhanced therapeutic results. Due to the promising practical clinical benefits that can be expected for the near future, an exposition to the practicing neurosurgeon about the basic issues in genetic therapy of gliomas seems convenient. Among the main topics, we shall discuss anti-tumoral mechanisms of various genes that can be transfected, the advantages and drawbacks of the different vectors utilized, the possibilities of tumor targeting by modifications in the native tropism of virus vectors, as well as the different physical methods for vector delivery to the tumors. Along with the exposition we will also review of the history of the genetic therapy for gliomas, with special focus on the main problems found during the advancement of scientific discoveries in this area. A general analysis is also made of the present state of this promising therapeutic modality, with reference to the problems that still must be solved and the new paradigms for future research in this area.

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Gene Therapy for Malignant Glioma Patients

Cited by 13 publications

References 9 publications

Recombinant adeno‐associated virus (rAAV) expressing TFPI‐2 inhibits invasion, angiogenesis and tumor growth in a human glioblastoma cell line

Recombinant adeno‐associated virus (rAAV) expressing TFPI‐2 inhibits invasion, angiogenesis and tumor growth in a human glioblastoma cell line

Systemic Vesicular Stomatitis Virus Selectively Destroys Multifocal Glioma and Metastatic Carcinoma in Brain

Genetic therapy in gliomas: Historical analysis and future perspectives

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