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Updated: Jul 29, 2026

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Molecular targeting of gene therapy and radiotherapy
R R Weichselbaum1, D W Kufe, S J Advani
1Department of Radiation and Cellular Oncology, The Pritzker School of Medicine, The University of Chicago, Illinois 60637, USA. rrw@rover.bsd.uchicago.edu
Abstract:
The full promise of gene therapy has been limited by the lack of specificity of vectors for tumor tissue as well as the lack of antitumor efficacy of transgenes encoded by gene delivery systems. In this paper we review our studies investigating two modifications of gene therapy combined with radiotherapy. The first investigations described include studies of radiation inducible gene therapy. In this paradigm, radio-inducible DNA sequences from the CarG elements of the Egr-1 promoter are cloned upstream of a cDNA encoding TNFalpha. The therapeutic gene (TNFalpha) is induced by radiation within the tumor microenvironment. In the second paradigm, genetically engineered herpes simplex virus (HSV-1) is induced by ionizing radiation to proliferate within the tumor volume. These modifications of radiotherapy and gene therapy may enhance the efficacy of both treatments.
Insights
This study explores combining gene therapy with radiotherapy to improve cancer treatment. Radiation-inducible gene therapy and engineered herpes simplex virus (HSV-1) show potential for enhanced antitumor efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Gene therapy's potential is hindered by poor tumor specificity and transgene efficacy.
- Radiotherapy is a cornerstone of cancer treatment but can affect healthy tissues.
Purpose of the Study:
- To investigate novel gene therapy strategies combined with radiotherapy for enhanced cancer treatment.
- To address limitations in current gene therapy delivery and efficacy.
Main Methods:
- Developed radiation-inducible gene therapy using Egr-1 promoter elements to drive TNFalpha expression in tumors.
- Engineered herpes simplex virus (HSV-1) to be selectively induced by ionizing radiation for tumor proliferation.
Main Results:
- Radiation-inducible gene therapy allows targeted transgene expression (TNFalpha) within the tumor microenvironment.
- Genetically modified HSV-1 demonstrates radiation-induced proliferation specifically within tumor volumes.
Conclusions:
- Combining radiotherapy with radiation-inducible gene therapy or engineered HSV-1 offers a promising approach to improve treatment efficacy.
- These synergistic strategies enhance both gene therapy delivery and radiotherapy's antitumor effects.
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