Gene Therapy for Human Nasopharyngeal Carcinoma by Adenovirus–Mediated Transfer of Human p53, GM-CSF, and B7-1 Genes in a Mouse Xenograft Tumor Model
| Autor: | Su-Ping Ren, Ying Han, Chu-Tse Wu, Li-Sheng Wang, Lan Wang, Bin Wu, Hua Wang |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Tumor suppressor gene T-Lymphocytes Genetic enhancement Cell Mice SCID Biology Adenoviridae Mice Cell Line Tumor medicine Animals Humans Cytotoxic T cell Radiology Nuclear Medicine and imaging Pharmacology Severe combined immunodeficiency Carcinoma Granulocyte-Macrophage Colony-Stimulating Factor Nasopharyngeal Neoplasms Genetic Therapy General Medicine medicine.disease Primary tumor Granulocyte macrophage colony-stimulating factor medicine.anatomical_structure Oncology Nasopharyngeal carcinoma B7-1 Antigen Cancer research Tumor Suppressor Protein p53 Neoplasm Transplantation T-Lymphocytes Cytotoxic medicine.drug |
| Zdroj: | Cancer Biotherapy and Radiopharmaceuticals. 23:591-602 |
| ISSN: | 1557-8852 1084-9785 |
| DOI: | 10.1089/cbr.2007.0447 |
| Popis: | Incidence of nasopharyngeal carcinoma (NPC) remains high in endemic regions. Prevention of tumor recurrences and metastases is a crucial approach to improve therapeutic outcome in NPC patients. In this study, we investigated the effects of the cotransfer of the tumor suppressor gene, p53, in combination with the immunostimulatory genes, GM-CSF and B7-1, on tumor regression and subsequent tumor recurrence. We constructed a recombinant adenovirus carrying human wild-type p53, granulocyte-macrophage colony-stimulating factor (GM-CSF), and B7-1 genes (Ad-p53/GM-CSF/B7-1), which mediated high-level expression of these three genes in NPC CNE-1 cells. Ad-p53/GM-CSF/B7-1 infection inhibited the growth of CNE-1 cells and induced tumor-specific cytotoxic T-lymphocytes (CTLs) in vitro. In CNE-1 xenograft tumor models in huPBL-nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice, an intratumoral injection of Ad-p53/GM-CSF/B7-1 resulted in a reduced tumor burden, compared to normal saline (NS) and Ad-p53 controls. Tumors in the Ad-p53/GM-CSF/B7-1 group displayed diffuse necrosis and infiltration of human T-cells. Further, the tumor occurrence of CNE-1 cell rechallenge largely decreased after the primary tumor was intratumorally injected with Ad-p53/GM-CSF/B7-1 in the HuPBL-NOD/SCID mice model. Only 2 of 8 (25%) animals in the Ad-p53/GM-CSF/B7-1 group had developed measurable tumors, which demonstrated extensive necrosis and much more human T-cell infiltration, compared to 5 of 7 (71%) in the NS and Ad-p53 groups. Therefore, the adenovirus-mediated introduction of p53, GM-CSF, and B7-1 genes could improve local control and prevent the recurrence or metastases of NPC tumors, which suggests a potential therapeutic value in NPC treatment. |
| Databáze: | OpenAIRE |
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