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Mediators of Inflammation
Volume 2013, Article ID 378971, 9 pages
http://dx.doi.org/10.1155/2013/378971
Research Article

Intricacies for Posttranslational Tumor-Targeted Cytokine Gene Therapy

1Department of Musculoskeletal Oncology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
2Department of Pediatrics, UT Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Unit 853, 1515 Holcombe Boulevard, Houston, TX 77030, USA

Received 30 August 2013; Accepted 30 October 2013

Academic Editor: Mohammad Athar

Copyright © 2013 Jeffry Cutrera et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The safest and most effective cytokine therapies require the favorable accumulation of the cytokine in the tumor environment. While direct treatment into the neoplasm is ideal, systemic tumor-targeted therapies will be more feasible. Electroporation-mediated transfection of cytokine plasmid DNA including a tumor-targeting peptide-encoding sequence is one method for obtaining a tumor-targeted cytokine produced by the tumor-bearing patient’s tissues. Here, the impact on efficacy of the location of targeting peptide, choice of targeting peptide, tumor histotype, and cytokine utilization are studied in multiple syngeneic murine tumor models. Within the same tumor model, the location of the targeting peptide could either improve or reduce the antitumor effect of interleukin (IL)12 gene treatments, yet in other tumor models the tumor-targeted IL12 plasmid DNAs were equally effective regardless of the peptide location. Similarly, the same targeting peptide that enhances IL12 therapies in one model fails to improve the effect of either IL15 or PF4 for inhibiting tumor growth in the same model. These interesting and sometimes contrasting results highlight both the efficacy and personalization of tumor-targeted cytokine gene therapies while exposing important aspects of these same therapies which must be considered before progressing into approved treatment options.