Abstract:
:We evaluated the therapeutic potential of the replication competent vector VA7-EGFP, which is based on the avirulent Semliki Forest virus (SFV) strain A7 (74) carrying the EGFP marker gene in an orthotopic lung cancer tumor model in nude mice. We have previously shown that this oncolytic vector destroys tumor cells efficiently in vitro and in vivo (in subcutaneous tumor model). Tumor growth in animals with orthotopically implanted adenocarcinoma cells (A549) were monitored during the study with small animal CT. We show that locally administered virotherapy with VA7-EGFP increased survival rate in experimental lung cancer significantly (p < 0.001) comparable to results obtained with the second generation conditionally replicating adenoviral vector Ad5-Delta24TK-GFP, used for comparison. The limited efficacy in systemically administered oncolytic viruses is the essential problem in oncolytic virotherapy and also in this study we were not able to elicit significant response with systemic administration route. Despite the fact that tumor microenvironment in orthotopic lung cancer is more optimal, viruses failed to home to the tumors and were unable to initiate efficient intratumoral replication. Clearly, the efficacy of virotherapy is influenced by many factors such as the route of virus administration, immunological and physiological barriers and cancer cell-specific features (IFN-responsiveness).
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Määttä AM,Mäkinen K,Ketola A,Liimatainen T,Yongabi FN,Vähä-Koskela M,Pirinen R,Rautsi O,Pellinen R,Hinkkanen A,Wahlfors Jdoi
10.1002/ijc.23646subject
Has Abstractpub_date
2008-10-01 00:00:00pages
1704-11issue
7eissn
0020-7136issn
1097-0215journal_volume
123pub_type
杂志文章abstract::Cryopreserved tumour cells obtained from the ascitic fluid of a patient with an ovarian carcinoma were employed to determine the effect on in vitro drug cytotoxicities of varying both drug concentration and exposure time. Four antitumour drugs, in common clinical usage, were selected for study. Tumour-cell survival fo...
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