Cytokine-induced killer cells carrying recombinant oncolytic adenovirus expressing p21Ras scFv inhibited liver cancer

Dai, Fang; Zhang, Peng-Bo; Feng, Qiang; Pan, Xin-Yan; Song, Shu-Ling; Cui, Jing; Yang, Ju-Lun

doi:10.7150/jca.51434

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J Cancer 2021; 12(9):2768-2776. doi:10.7150/jca.51434 This issue Cite

Research Paper

Cytokine-induced killer cells carrying recombinant oncolytic adenovirus expressing p21Ras scFv inhibited liver cancer

Fang Dai^1,2#, Peng-Bo Zhang^3#, Qiang Feng², Xin-Yan Pan², Shu-Ling Song², Jing Cui², Ju-Lun Yang^1,2✉

1. Graduate School, Kunming Medical University, Kunming, Yunnan, China.
2. 920 th Hospital of the Joint Logistics Support Force of PLA, Kunming, Yunnan, China.
3. Medical School, Kunming University of Science and Technology, Kunming, Yunnan, China.
#Co-first authors.

Citation:

Dai F, Zhang PB, Feng Q, Pan XY, Song SL, Cui J, Yang JL. Cytokine-induced killer cells carrying recombinant oncolytic adenovirus expressing p21Ras scFv inhibited liver cancer. J Cancer 2021; 12(9):2768-2776. doi:10.7150/jca.51434. https://www.jcancer.org/v12p2768.htm

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Abstract

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.

Keywords: oncolytic adenovirus, Ras, liver cancer, CIK, scFv

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APA

Dai, F., Zhang, P.B., Feng, Q., Pan, X.Y., Song, S.L., Cui, J., Yang, J.L. (2021). Cytokine-induced killer cells carrying recombinant oncolytic adenovirus expressing p21Ras scFv inhibited liver cancer. Journal of Cancer, 12(9), 2768-2776. https://doi.org/10.7150/jca.51434.

ACS

Dai, F.; Zhang, P.B.; Feng, Q.; Pan, X.Y.; Song, S.L.; Cui, J.; Yang, J.L. Cytokine-induced killer cells carrying recombinant oncolytic adenovirus expressing p21Ras scFv inhibited liver cancer. J. Cancer 2021, 12 (9), 2768-2776. DOI: 10.7150/jca.51434.

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CSE

Dai F, Zhang PB, Feng Q, Pan XY, Song SL, Cui J, Yang JL. 2021. Cytokine-induced killer cells carrying recombinant oncolytic adenovirus expressing p21Ras scFv inhibited liver cancer. J Cancer. 12(9):2768-2776.

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