Osteosarcoma and chondrosarcoma as targets for virus vectors and herpes simplex virus thymidine kinase/ganciclovir gene therapy

Ketola, Anna; Määttä, Ann-Marie; Pasanen, Tiina; Tulimäki, Kirsi; Wahlfors, Jarmo

doi:10.3892/ijmm.13.5.705

Cited by 18 publications

(21 citation statements)

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“…Our results indicated that increasing the percentage of Ad-TK transfected cells (1, 5, 10, or 20%) in the cell mixture resulted in a significant increase in cell death (20,63,76, and 97%, re- …”

Section: Bystander Killing Effect Of Ad-tk/gcv Treatment In Leiomyomamentioning

confidence: 80%

Gene Therapy of Uterine Leiomyoma: Adenovirus-Mediated Herpes Simplex Virus Thymidine Kinase/Ganciclovir Treatment Inhibits Growth of Human and Rat Leiomyoma Cells in vitro and in a Nude Mouse Model

Salama¹,

Kamel²,

Christman

et al. 2006

Gynecol Obstet Invest

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Uterine leiomyomas (LM) affect a high percentage of reproductive-age women. They develop as discrete, well-defined tumors that are easily accessible with imaging techniques – making this disease ideal for localized gene therapy approaches. In this study, we determined the efficacy of adenovirus-mediated herpes simplex virus thymidine kinase gene transfer in combination with ganciclovir (Ad-TK/GCV) as a potential therapy for LM. Rat ELT-3 LM cells and human LM cells were transfected with different multiplicity of infections (10–100 plaque forming units [PFU]/cell) of Ad-TK and treated with GCV (5, 10, or 20 µg/ml) for 5 days. To test the bystander effect, Ad-TK-transfected ELT-3 cells (100 PFU/cell) or LM cells (10 PFU/cell) were cocultured with corresponding nontransfected cells at increasing percentages and treated with GCV followed by cell counting. In ELT-3 cells transfected with Ad-TK/GCV (10, 20, 50, or 100 PFU/cell), the cell count was reduced by 24, 42, 77, and 87%, respectively, compared with the control cells (transfected with Ad-Lac Z/GCV). Similarly, in LM cells transfected with Ad-TK/GCV (10, 50, or 100 PFU/cell), the cell count was reduced by 31, 62, and 82%, respectively, compared with the control. A strong bystander effect was noted in both ELT-3 and LM cells with significant killing (p = 0.001) at a ratio of infected:uninfected cells of only 1:99 and maximal killing at 1:4. This study demonstrates the potential efficacy of the Ad-TK/GCV gene therapy approach as a viable nonsurgical alternative treatment for uterine LM.

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Section: Bystander Killing Effect Of Ad-tk/gcv Treatment In Leiomyomamentioning

confidence: 80%

Gene Therapy of Uterine Leiomyoma: Adenovirus-Mediated Herpes Simplex Virus Thymidine Kinase/Ganciclovir Treatment Inhibits Growth of Human and Rat Leiomyoma Cells in vitro and in a Nude Mouse Model

Salama¹,

Kamel²,

Christman

et al. 2006

Gynecol Obstet Invest

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“…With the use of ex vivo transduced tumor cells inoculated in xenografts on a rat hind limb, they showed that this system reduced the tumor mass and prevented the appearance of lung metastases (15). In addition, Ketola et al studied the efficacy of adenoviral/lentiviral delivery for HSV-TK/GCV gene therapy in OS cell lines and reported sufficient HSV-TK expression yielding both cytotoxicity and a bystander effect (67). They reported that the cell lines tested were transduced at high efficiency and that HSV-TK expression was comparable to that with adenovirus vectors.…”

Section: Suicide Gene Therapymentioning

confidence: 99%

Evolving gene therapy approaches for osteosarcoma using viral vectors: Review

Witlox

Lamfers

Wuisman

et al. 2007

Bone

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“…However, the fetal case report following adenovirus gene transfer (75) indicated against this strategy in humans. As other than adenovirus gene transfer vectors, it has been shown that osteosarcoma cell lines were good targets for lentiviral transduction with favorable gene transfer efficiency (76,77). After the development of a successful and safe delivery of the therapeutic gene, this strategy demonstrates great potential activity to modulate the prognosis of patients with osteosarcoma.…”

Section: Gene Therapy Eliciting Immune Response In Tumor-bearing Hostmentioning

confidence: 99%

Osteosarcoma: Current status of immunotherapy and future trends (Review)

Mori¹,

Rédini²,

Cherrier³

et al. 2006

Oncol Rep

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Abstract. Osteosarcoma is the most common primary bone tumor and represents a major therapeutic challenge in medical oncology. While the use of aggressive chemotherapy has drastically improved the prognosis of the patients with nonmetastatic osteosarcomas, the very poor prognosis of patients with metastasis have led to the exploration of new, more effective and less toxic treatments, such as immunotherapy for curing osteosarcoma. Compared to the numerous reports describing successful immunotherapy for other solid tumors, the number of reports concerning immunotherapy for osteosarcoma is low. However, this therapeutic strategy opens new areas for the treatment of osteosarcoma. In this review, the reasons for delay and all elements essential to develop immunotherapy concerning osteosarcoma are defined. Several pieces of evidence strongly support the potential capability of new therapies such as cellular therapy and gene therapy to eradicate osteosarcoma. Thus, clinical human trials using peptides, cytokines and dendritic cells have been performed. Tumor-infiltrating lymphocytes and some tumor antigens have been identified in osteosarcoma and resulted in an important breakthrough in cellular immunotherapy. Also, RANKL/RANK/OPG, the key regulator of bone metabolism, is a hot spot in this field as therapeutic tools. Immunotherapy for osteosarcomas has great potential, promising improvement in the survival rate and better quality of life for the patients.

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Osteosarcoma and chondrosarcoma as targets for virus vectors and herpes simplex virus thymidine kinase/ganciclovir gene therapy

Cited by 18 publications

References 0 publications

Gene Therapy of Uterine Leiomyoma: Adenovirus-Mediated Herpes Simplex Virus Thymidine Kinase/Ganciclovir Treatment Inhibits Growth of Human and Rat Leiomyoma Cells in vitro and in a Nude Mouse Model

Gene Therapy of Uterine Leiomyoma: Adenovirus-Mediated Herpes Simplex Virus Thymidine Kinase/Ganciclovir Treatment Inhibits Growth of Human and Rat Leiomyoma Cells in vitro and in a Nude Mouse Model

Evolving gene therapy approaches for osteosarcoma using viral vectors: Review

Osteosarcoma: Current status of immunotherapy and future trends (Review)

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