%0 Journal Article
%T Intricacies for Posttranslational Tumor-Targeted Cytokine Gene Therapy
%A Jeffry Cutrera
%A Denada Dibra
%A Arun Satelli
%A Xuexing Xia
%A Shulin Li
%J Mediators of Inflammation
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/378971
%X 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. 1. Introduction Immunotherapy is one of the most promising treatment strategies for cancer and other diseases; however, several obstacles need to be overcome before immunotherapies are widely accepted in the clinics. Several cytokines and chemokines, such as interleukin (IL) 2 [1, 2], interferon (IFN) ¦Á [3], IL12 [4¨C8], IL15 [9¨C12], and chemokine platelet factor 4 (PF4) [13¨C15], are very effective for inhibiting tumor growth via immunomodulatory mechanisms in mouse models, and dozens of either active or completed clinical trials utilize cytokines alone or as an adjuvant for treating cancer [16]. However, only IL-2 and IFN¦Á have been approved by the FDA for the treatment of a small subset of cancers, and these therapies are only administered systemically in recombinant protein form [17]. One strategy that may soon help improve these therapies is gene therapy, the administration of DNA which encodes for a therapeutic protein. Although not ideal for producing all types of therapeutic proteins, the increase in safety and efficacy while reducing costs makes immune gene therapies feasible [18¨C20]. For most immune gene therapies the gene product must be located in the tumor microenvironment to be most
%U http://www.hindawi.com/journals/mi/2013/378971/