Jan, 2017
Distant Bystander Effect of REIC/DKK3 Gene Therapy Through Immune System Stimulation in Thoracic Malignancies
ANTICANCER RESEARCH
- Volume
- 37
- Number
- 1
- First page
- 301
- Last page
- 307
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.21873/anticanres.11321
- Publisher
- INT INST ANTICANCER RESEARCH
Background: Reduced expression in immortalized cell (REIC)/Dickkoph-3 (DKK3) is a tumor-suppressor gene, and its overexpression by adenovirus vector (Ad-REIC) exhibits a remarkable therapeutic effect on various human cancer types through a mechanism triggered by endoplasmic reticulum stress. Materials and Methods: We examined the direct anti-tumor effect of Ad-REIC gene therapy on lung cancer and malignant mesothelioma cell lines in vitro, and the distant bystander effect using immunocompetent mouse allograft models with bilateral flank tumors. Results: Ad-REIC treatment showed antitumor effect in many lung cancer and malignant mesothelioma cell lines in vitro. In an in vivo model, Ad-REIC treatment inhibited the growth not only of directly treated tumors but also of distant untreated tumors. By immunohistochemical analysis, infiltration of T-cells and natural killer (NK) cells and expression of the major histocompatibility complex (MHC) class I molecules were observed in bilateral tumors. Conclusion: Ad-REIC treatment not only had a direct antitumor effect but also an indirect bystander effect through stimulation of the immune system.
- Link information
- ID information
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- DOI : 10.21873/anticanres.11321
- ISSN : 0250-7005
- eISSN : 1791-7530
- Pubmed ID : 28011506
- Web of Science ID : WOS:000391958800040