Intricacies for Posttranslational Tumor-Targeted Cytokine Gene Therapy

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 incl...

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Main Authors: Jeffry Cutrera, Denada Dibra, Arun Satelli, Xuexing Xia, Shulin Li
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2013/378971
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author Jeffry Cutrera
Denada Dibra
Arun Satelli
Xuexing Xia
Shulin Li
author_facet Jeffry Cutrera
Denada Dibra
Arun Satelli
Xuexing Xia
Shulin Li
author_sort Jeffry Cutrera
collection DOAJ
description 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.
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spelling doaj-art-9b2ba3deb4bd4d6ebb04dbd9d57a99d72025-02-03T06:44:23ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/378971378971Intricacies for Posttranslational Tumor-Targeted Cytokine Gene TherapyJeffry Cutrera0Denada Dibra1Arun Satelli2Xuexing Xia3Shulin Li4Department of Musculoskeletal Oncology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Pediatrics, UT Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Unit 853, 1515 Holcombe Boulevard, Houston, TX 77030, USADepartment of Pediatrics, UT Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Unit 853, 1515 Holcombe Boulevard, Houston, TX 77030, USADepartment of Pediatrics, UT Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Unit 853, 1515 Holcombe Boulevard, Houston, TX 77030, USADepartment of Pediatrics, UT Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Unit 853, 1515 Holcombe Boulevard, Houston, TX 77030, USAThe 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.http://dx.doi.org/10.1155/2013/378971
spellingShingle Jeffry Cutrera
Denada Dibra
Arun Satelli
Xuexing Xia
Shulin Li
Intricacies for Posttranslational Tumor-Targeted Cytokine Gene Therapy
Mediators of Inflammation
title Intricacies for Posttranslational Tumor-Targeted Cytokine Gene Therapy
title_full Intricacies for Posttranslational Tumor-Targeted Cytokine Gene Therapy
title_fullStr Intricacies for Posttranslational Tumor-Targeted Cytokine Gene Therapy
title_full_unstemmed Intricacies for Posttranslational Tumor-Targeted Cytokine Gene Therapy
title_short Intricacies for Posttranslational Tumor-Targeted Cytokine Gene Therapy
title_sort intricacies for posttranslational tumor targeted cytokine gene therapy
url http://dx.doi.org/10.1155/2013/378971
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AT xuexingxia intricaciesforposttranslationaltumortargetedcytokinegenetherapy
AT shulinli intricaciesforposttranslationaltumortargetedcytokinegenetherapy