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Gene transfer of pro-IL-18 and IL-1β converting enzyme cDNA induces potent antitumor effects in L1210 cells

Leukemia volume 18, pages 817–825 (2004)Cite this article

Abstract

We report in a murine model of acute lymphoid leukemia L1210 the potent antitumor efficiency of a combinatorial delivery of pro-IL-18 gene modified L1210 (Lp18) and IL-1β converting enzyme (ICE) gene modified L1210 (LpICE). Live leukemia cells Lp18 or Lp18 plus LpICE showed apparently reduced leukemogenicity with a survival rate of 40 or 50% at 50 days after intraperitoneal (i.p.) inoculation of a lethal dose of cells, respectively. Combination of Lp18 and LpICE was capable of inhibiting accumulation of bloody ascites, synergistically superior to Lp18 or LpICE alone. All surviving mice were rechallenged with parental L1210 cells at day 50, and all survived up to day 80, suggesting that gene-modified cells induced immune protection. Moreover, NK cytotoxicity and CTL activity were both enhanced in mice injected with Lp18, especially Lp18 plus LpICE. Levels of IFN-γ were not altered significantly by inoculation of Lp18 or Lp18 plus LpICE. Our results demonstrate that IL-18 is a useful candidate gene in gene therapy of lymphoma or lymphoid leukemia, and ex vivo combinatorial delivery of Lp18 plus LpICE either as a single approach or as an adjunct to concomitant radiotherapy or chemotherapy, may be more efficient in a situation of minimal residual disease.

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Acknowledgements

This work was supported by the Climbing Program granted by The Ministry of Science and Technology of China (95-special-10) and the Tianjin Science and Technology Development program of China (003119311). Thanks to Ms. Yi-Qi Geng, Li-Li An, Min Wang, and Mrs Xiu-Jun Zhang, Ying-Hua Yang, Jun-Ming Zhao for their technical assistance. Thanks to Professor Sheng-Guo You for kindly providing L1210 and YAC-1 cells.

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  1. National Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

    B Zhang, K-F Wu, Y-M Lin, X-T Ma, Q Rao, G-G Zheng, Z-Y Cao, G Li & Y-H Song

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Zhang, B., Wu, KF., Lin, YM. et al. Gene transfer of pro-IL-18 and IL-1β converting enzyme cDNA induces potent antitumor effects in L1210 cells. Leukemia 18, 817–825 (2004). https://doi.org/10.1038/sj.leu.2403320

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