Suicide gene therapy for plasma cell tumors

Suicide gene therapy for plasma cell tumors was attempted in severe combined immunodeficient (SCID) mice injected with human myeloma cell lines. Initially, a ganciclovir-induced bystander effect was observed in vitro using myeloma cells transduced with a herpes simplex thymidine kinase (HSVtk) gene. Transduced cells injected subcutaneously (SC) into SCID mice could be eradicated by the administration of ganciclovir (GCV). Furthermore, an in vivo bystander effect was noticed when mice received mixtures of HSVtk-positive and nontransduced cells. Unexpectedly, a “distant bystander” effect was observed as tumors in regions inoculated with only nontransduced cells were significantly smaller and had increased frequency of apoptotic figures and decreased mitotic frequency in GCV-treated mice transplanted with HSVtk-positive cells at a different region compared with control mice.

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590. SuperCD Enables Low Dose 5-FC Application for Effective Suicide Gene Therapy in a Rat Hepatoma Model Both In Vitro and In Vivo

Molecular Therapy ◽

10.1016/j.ymthe.2004.06.517 ◽

2004 ◽

Vol 9 ◽

pp. S223

Keyword(s):

Gene Therapy ◽

Low Dose ◽

Suicide Gene ◽

Suicide Gene Therapy ◽

Hepatoma Model ◽

Rat Hepatoma

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Suicide Gene Therapy By Amphiphilic Copolymer Nanocarrier for Spinal Cord Tumor

Nanomaterials ◽

10.3390/nano9040573 ◽

2019 ◽

Vol 9 (4) ◽

pp. 573 ◽

Cited By ~ 3

Author(s):

So-Jung Gwak ◽

Jeoung Soo Lee

Keyword(s):

Spinal Cord ◽

Gene Therapy ◽

Spinal Cord Tumor ◽

Suicide Gene ◽

Amphiphilic Copolymer ◽

Suicide Gene Therapy ◽

Gene Carrier ◽

C6 Cells

Spinal cord tumors (SCT) are uncommon neoplasms characterized by irregular growth of tissue inside the spinal cord that can result in non-mechanical back pain. Current treatments for SCT include surgery, radiation therapy, and chemotherapy, but these conventional therapies have many limitations. Suicide gene therapy using plasmid encoding herpes simplex virus-thymidine kinase (pHSV-TK) and ganciclovir (GCV) has been an alternative approach to overcome the limitations of current therapies. However, there is a need to develop a carrier that can deliver both pHSV-TK and GCV for improving therapeutic efficacy. Our group developed a cationic, amphiphilic copolymer, poly (lactide-co-glycolide) -graft-polyethylenimine (PgP), and demonstrated its efficacy as a drug and gene carrier in both cell culture studies and animal models. In this study, we evaluated PgP as a gene carrier and demonstrate that PgP can efficiently deliver reporter genes, pGFP in rat glioma (C6) cells in vitro, and pβ-gal in a rat T5 SCT model in vivo. We also show that PgP/pHSV-TK with GCV treatment showed significantly higher anticancer activity in C6 cells compared to PgP/pHSV-TK without GCV treatment. Finally, we demonstrate that PgP/pHSV-TK with GCV treatment increases the suicide effect and apoptosis of tumor cells and reduces tumor size in a rat T5 SCT model.

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