| Effect of suicide gene therapy in combination with immunotherapy on antitumour immune response & tumour regression in a xenograft mouse model for head & neck squamous cell carcinoma. | |
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MedLine Citation:
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PMID: 20966520 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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BACKGROUND & OBJECTIVES: Prodrug activation strategy as well as immunotherapy have been widely used for cancer gene therapy. In the present study, using a head and neck squamous cell carcinoma (HNSCC) xenograft nude mouse model, we have investigated whether the two therapies in combination could improve tumour cell kill. We also investigated induction of immune effector cells viz., NK (DX5+) and DC (CD11c+) in vivo, post-combination gene therapy. METHODS: A retroviral vector producing cell line (PLTK47.1 VPC) carrying Herpes simplex virus thymidine kinase gene (HSVtk) was used for intratumoural injection into NT8e xenograft tumours followed by the prodrug ganciclovir (GCV). IL-2 plasmid DNA was injected intramuscularly. Immune cells were analyzed by flow-cytometry. Non parametric ANOVA was performed with Kruskal Wallis test. RESULTS: IL-2 could induce proliferation of both NK cells (DX5+) and dendritic cells (CD11c+) in vivo. Apoptosis was higher in combination therapy group as compared to HSVtk/GCV alone or IL-2 alone and was mediated through caspase-3 dependent pathway. Significant reduction in tumour volume was seen in all 3 treatment arms as compared to controls. INTERPRETATION & CONCLUSIONS: Combination of suicide gene therapy and immunotherapy leads to successful tumour regression in a HNSCC xenograft mouse model. Immunotherapy could help in a systemic long lived anti-tumour immune response which would prove powerful for the treatment of metastatic cancers, and also for minimal residual disease. The results of this study may form the basis for Phase 1 clinical trials. |
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Authors:
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Aditya V Ambade; Ganesh V Joshi; Rita Mulherkar |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Indian journal of medical research Volume: 132 ISSN: 0971-5916 ISO Abbreviation: Indian J. Med. Res. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0374701 Medline TA: Indian J Med Res Country: India |
Other Details:
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Languages: eng Pagination: 415-22 Citation Subset: IM |
Affiliation:
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Advanced Center for Treatment Research & Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, India. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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