期刊
JOURNAL OF CANCER
卷 12, 期 9, 页码 2768-2776出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.51434
关键词
oncolytic adenovirus; Ras; liver cancer; CIK; scFv
类别
资金
- Major Science and Technology Project of the Yunnan Science and Technology Plan [2018ZF009]
- Applied Basic Research Project of 920th Hospital of Joint Logistics Support Force [2019YGB02]
- National Natural Science Foundation of China [81460464]
A novel strategy combining oncolytic adenovirus with CIK cells for treating Ras-driven liver cancer was developed. The in vivo study showed significantly inhibited tumor growth with little effect on normal organs, indicating relative safety.
Background: Oncolytic adenovirus-mediated gene therapy is an emerging strategy for cancer treatment. However, oncolytic adenoviruses are mainly administered locally at tumor site. Intravenous administration of oncolytic adenovirus for cancer gene therapy is a problem that needs to be solved urgently. Methods: We constructed recombinant oncolytic adenovirus KGHV500 carrying anti-p21Ras scFv and employed CIK cells to deliver KGHV500. TUNEL, wound healing, MTT, and Transwell invasion assays were used to determine the anti-tumor efficacy of KGHV500 on liver cancer cells in vitro. Nude mouse xenograft model was used to examine the anti-tumor efficacy of CIK cells combined with KGHV500 in vivo. Furthermore, KGHV500 accumulation in different organs was detected to assess the safety. Results: KGHV500 inhibited the migration, proliferation, invasion, and induced the apoptosis of liver cancer cells. CIK cells carrying KGHV500 reached tumor site and exerted much better anti-tumor efficacy than CIK cells or KGHV500 alone in nude mouse xenograft model. Moreover, we detected KGHV500 and anti-p21Ras scFv in different organs of nude mice, with little effects on the organs. Conclusions: We develop a novel strategy for the treatment of Ras-driven liver cancer by combining CIK cells with oncolytic adenovirus expressing anti-p21Ras scFv. Intravenous injection of CIK cells carrying KGHV500 in vivo significantly inhibits tumor growth, has little effect on normal organs, and is relatively safe.
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