Marina N Torrero1, William G Henk, Shulin Li. 1. Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
Abstract
PURPOSE: Bleomycin electrochemotherapy has been successfully used in preclinical studies and clinical trials for treating squamous cell carcinoma (SCC) and adenocarcinoma; however, it is not effective for treating recurrent tumors or metastatic tumors, or for preventing tumor redevelopment. In this study, we explore the coadministration of bleomycin and interleukin-12 (IL-12) followed by electroporation for treating primary and metastatic tumors. EXPERIMENTAL DESIGN: Bleomycin, IL-12 plasmid DNA, or a combination of both were injected into high-grade malignant mammary tumors and SCCVII followed by electroporation. The tumor growth, survival, metastasis in lungs, CTL activity, and vascular density were analyzed. The results were analyzed by the two-sided Student's t test and Gehan's Wilcoxon test. RESULTS: Coadministration of bleomycin and IL-12 via electroporation eradicates preestablished 4T1 mammary tumors in up to 60% of mice, inhibits metastatic tumor development, and extends the long-term survival. Likewise, coadministration of bleomycin and IL-12 via electroporation eradicates squamous cell carcinoma (SCCVII) in 100% of mice and prevents tumor redevelopment in 80% of mice. Neither bleomycin nor IL-12 alone is able to achieve the same therapeutic potency. The primary role of bleomycin is to inhibit the tumor vessel development; the primary role of IL-12 is to increase the immune response that extends the survival of treated mice and inhibits the tumor redevelopment. CONCLUSIONS: This combination modality has great potential to be translated in a clinical setting for treating high-grade malignancies and for preventing tumor redevelopment.
PURPOSE:Bleomycin electrochemotherapy has been successfully used in preclinical studies and clinical trials for treating squamous cell carcinoma (SCC) and adenocarcinoma; however, it is not effective for treating recurrent tumors or metastatic tumors, or for preventing tumor redevelopment. In this study, we explore the coadministration of bleomycin and interleukin-12 (IL-12) followed by electroporation for treating primary and metastatic tumors. EXPERIMENTAL DESIGN:Bleomycin, IL-12 plasmid DNA, or a combination of both were injected into high-grade malignant mammary tumors and SCCVII followed by electroporation. The tumor growth, survival, metastasis in lungs, CTL activity, and vascular density were analyzed. The results were analyzed by the two-sided Student's t test and Gehan's Wilcoxon test. RESULTS: Coadministration of bleomycin and IL-12 via electroporation eradicates preestablished 4T1 mammary tumors in up to 60% of mice, inhibits metastatic tumor development, and extends the long-term survival. Likewise, coadministration of bleomycin and IL-12 via electroporation eradicates squamous cell carcinoma (SCCVII) in 100% of mice and prevents tumor redevelopment in 80% of mice. Neither bleomycin nor IL-12 alone is able to achieve the same therapeutic potency. The primary role of bleomycin is to inhibit the tumor vessel development; the primary role of IL-12 is to increase the immune response that extends the survival of treated mice and inhibits the tumor redevelopment. CONCLUSIONS: This combination modality has great potential to be translated in a clinical setting for treating high-grade malignancies and for preventing tumor redevelopment.
Authors: S Tugues; S H Burkhard; I Ohs; M Vrohlings; K Nussbaum; J Vom Berg; P Kulig; B Becher Journal: Cell Death Differ Date: 2014-09-05 Impact factor: 15.828
Authors: Q Li; X H Yang; F Xu; C Sharma; H-X Wang; K Knoblich; I Rabinovitz; S R Granter; M E Hemler Journal: Oncogene Date: 2012-07-23 Impact factor: 9.867