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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Wiley
2013-01-01
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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. |
format | Article |
id | doaj-art-9b2ba3deb4bd4d6ebb04dbd9d57a99d7 |
institution | Kabale University |
issn | 0962-9351 1466-1861 |
language | English |
publishDate | 2013-01-01 |
publisher | Wiley |
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series | Mediators of Inflammation |
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 |
work_keys_str_mv | AT jeffrycutrera intricaciesforposttranslationaltumortargetedcytokinegenetherapy AT denadadibra intricaciesforposttranslationaltumortargetedcytokinegenetherapy AT arunsatelli intricaciesforposttranslationaltumortargetedcytokinegenetherapy AT xuexingxia intricaciesforposttranslationaltumortargetedcytokinegenetherapy AT shulinli intricaciesforposttranslationaltumortargetedcytokinegenetherapy |