Cytokine gene therapy using adenovirally transduced, tumor-seeking activated natural killer cells
- PMID: 17678438
- DOI: 10.1089/hum.2007.052
Cytokine gene therapy using adenovirally transduced, tumor-seeking activated natural killer cells
Abstract
We previously demonstrated that adoptively transferred, interleukin (IL)-2-activated natural killer (A-NK) cells are effective in reducing B16 lung tumors in tumor-bearing animals. This effect depends on high and often toxic doses of IL-2 to support the survival and antitumor functions of the transferred A-NK cells. We hypothesized that A-NK cells transduced to express pro-NK cell cytokines would become less dependent on high and potentially toxic amounts of IL-2. Here, we demonstrate that A-NK cells adenovirally transduced to express mIL-12 survive well and function efficiently in mice bearing B16 lung tumors when supported with low, nontoxic doses of IL-2. The intratumoral survival of nontransduced "bystander'' A-NK cells also increased when they were coinjected with IL-12 gene-transduced A-NK cells. The enhanced survival of exogenously delivered, IL-12 gene-transduced A-NK cells resulted in greater antitumor responsiveness. This led to a 7- to 10-day increase in median survival time compared with tumor-bearing mice receiving mock-transduced A-NK cells. These data show that the presence of IL-12 around tumor-infiltrating A-NK cells enhances their antitumor activity while reducing their requirement for systemically administered IL-2.
Similar articles
-
Targeting of products of genes to tumor sites using adoptively transferred A-NK and T-LAK cells.Cancer Gene Ther. 2007 May;14(5):441-50. doi: 10.1038/sj.cgt.7701019. Epub 2007 Feb 2. Cancer Gene Ther. 2007. PMID: 17273184
-
An IL-12/Shh-C domain fusion protein-based IL-12 autocrine loop for sustained natural killer cell activation.Int J Oncol. 2012 Aug;41(2):661-9. doi: 10.3892/ijo.2012.1466. Epub 2012 May 8. Int J Oncol. 2012. PMID: 22581115
-
Endogenous IL-2 production by natural killer cells maintains cytotoxic and proliferative capacity following retroviral-mediated gene transfer.Exp Hematol. 1997 Oct;25(11):1140-8. Exp Hematol. 1997. PMID: 9328450
-
Harnessing NK Cell Memory for Cancer Immunotherapy.Trends Immunol. 2016 Dec;37(12):877-888. doi: 10.1016/j.it.2016.09.005. Epub 2016 Oct 21. Trends Immunol. 2016. PMID: 27773685 Free PMC article. Review.
-
Gene therapy approaches against cancer using in vivo and ex vivo gene transfer of interleukin-12.Immunotherapy. 2016 Feb;8(2):179-98. doi: 10.2217/imt.15.109. Epub 2016 Jan 20. Immunotherapy. 2016. PMID: 26786809 Review.
Cited by
-
Adoptive transfer of natural killer cells promotes the anti-tumor efficacy of T cells.Clin Immunol. 2017 Apr;177:76-86. doi: 10.1016/j.clim.2016.06.013. Epub 2016 Jul 1. Clin Immunol. 2017. PMID: 27377534 Free PMC article.
-
Lentiviral gene transduction in human and mouse NK cell lines.Methods Mol Biol. 2010;612:209-21. doi: 10.1007/978-1-60761-362-6_14. Methods Mol Biol. 2010. PMID: 20033643 Free PMC article.
-
Inhibition of intracellular antiviral defense mechanisms augments lentiviral transduction of human natural killer cells: implications for gene therapy.Hum Gene Ther. 2012 Oct;23(10):1090-100. doi: 10.1089/hum.2012.080. Epub 2012 Sep 10. Hum Gene Ther. 2012. PMID: 22779406 Free PMC article.
-
NK cells in the tumor microenvironment.Crit Rev Oncog. 2014;19(1-2):91-105. doi: 10.1615/critrevoncog.2014011142. Crit Rev Oncog. 2014. PMID: 24941376 Free PMC article. Review.
-
Adoptive Cell Transfer: Is it a Promising Immunotherapy for Colorectal Cancer?Theranostics. 2018 Nov 10;8(20):5784-5800. doi: 10.7150/thno.29035. eCollection 2018. Theranostics. 2018. PMID: 30555581 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
