期刊
MOLECULAR CANCER THERAPEUTICS
卷 8, 期 1, 页码 141-151出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-08-0533
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资金
- Genelux
- NIH [R01 CA 75416, R01 CA/DK80982]
- Susan G. Komen Breast Cancer Foundation [IMG0402501]
- Flight Attendant Medical Research Institute [032047]
- NATIONAL CANCER INSTITUTE [R01CA075416, R01CA080982] Funding Source: NIH RePORTER
Oncolytic virotherapy of tumors has shown promising results in both preclinical and clinical studies. Here, we investigated the therapeutic efficacy of a replication-competent vaccinia virus, GLV-1h68, against human pancreatic carcinomas in cell cultures and in nude mice. We found that GLV-1h68 was able to infect, replicate in, and lyse tumor cells in vitro. Virus-mediated marker gene expressions were readily detected. Moreover, s.c. PANC-1 pancreatic tumor xenografts were effectively treated by a single i.v. dose of GLV-1h68. Cancer killing was achieved with minimal toxicity. Viral titer analyses in homogenized organs and PANC-1 tumors showed that the mutant virus resides almost exclusively in the tumors and not in healthy organs. Except mild spleen enlargements, no histopathology changes were observed in any other organs 2 months after virus injection. Surprisingly, s.c. MIA PaCa-2 pancreatic tumors were treated with similar efficiency as PANC-1 tumors, although they differ significantly in sensitivity to viral lysis in cell cultures. When GLV-1h68 oncolytic viral therapy was used together with cisplatin or gemcitabine to treat PANC-1 tumors, the combination therapy resulted in enhanced and accelerated therapeutic results compared with the virus treatment alone. Profiling of proteins related to immune response revealed a significant proinflammatory immune response and marked activation of innate immunity in virus-colonized tumors. In conclusion, the GLV-1h68 strain showed outstanding therapeutic effects and a documented safety profile in mice, with great promise for future clinical development. [Mol Cancer Ther 2009;8(1): 141 - 51]
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