In vitro and in vivo antitumor effects of the recombinant immunotoxin IL6(T23)-PE38KDEL in multiple myeloma

Guo,De-Jun; Han,Jia-Shan; Li,Yan-Song; Liu,Zeng-Shan; Lu,Shi-Ying; Ren,Hong-Lin

doi:10.3892/ol.2012.733

In vitro and in vivo antitumor effects of the recombinant immunotoxin IL6(T23)-PE38KDEL in multiple myeloma

Authors:
- De-Jun Guo
- Jia-Shan Han
- Yan-Song Li
- Zeng-Shan Liu
- Shi-Ying Lu
- Hong-Lin Ren
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Affiliations: College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin 130062, P.R. China, College of Food, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China, Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, Jilin 130062, P.R. China
Published online on: May 25, 2012 https://doi.org/10.3892/ol.2012.733
Pages: 311-318

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Abstract

IL6(T23)-PE38KDEL is a chimeric molecule composed of interleukin 6 (IL6), missing the N-terminal 23 amino acids, and fused to a truncated mutant form of Pseudomonas exotoxin (PE38KDEL). The aim of this study was to evaluate this recombinant immunotoxin in terms of its specific cytotoxicity to IL6R-overexpressing multiple myeloma (MM) cells in vitro, as well as its antitumor effects and side effects in vivo. IL6(T23)-PE38KDEL was expressed in Escherichia coli, refolded and purified from inclusion bodies. The purified IL6(T23)-PE38KDEL was found to be selectively cytotoxic to IL6 receptor-positive tumor cells in vitro. IC50 values of IL6(T23)-PE38KDEL were evaluated by MTS assay. Toxicity and maximum-tolerated dose of IL6(T23)-PE38KDEL were determined in mice. The antitumor activity of IL6(T23)-PE38KDEL was evaluated in mice with MM through intravenous injection and interventional therapy. Intravenous administration of IL6(T23)-PE38KDEL caused a significantly increased survival time in treated mice, and exhibited dose- and time-dependent antitumor effects against MM mice. Moreover, complete tumor regression was observed in 30 and 80% of mice treated intravenously and intraperitoneally, respectively, with 0.4 mg/kg/day for 10 days. These results demonstrated that the recombinant immunotoxin IL6(T23)-PE38KDEL kills IL6R-overexpressing cancer cells, and causes significant tumor regression.

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