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[The protocol of clinical trial and basic experiments for esophageal cancer using gene transduction]
1Department of Surgery II, Chiba University School of Medicine.
Abstract:
We examined whether antitumor effect could be produced by retrovirally expressed interleukin-2(IL-2) gene, glanulocyte macrophage-colony stimulating factor(GM-CSF) gene, herpes simplex virus-thymidine kinase(HSV-tk) gene and p53 gene in human esophageal cancer cells using nude mice. Loss of tumorigenicity of IL-2 or GM-CSF producing cancer cells were observed. The antitumor effect was also evidenced by the injection of these cells into established tumors of wild-type cells. In suicide gene therapy on esophageal cancer, the growth suppression of esophageal cancer cells transducing HSV-tk gene tumors in nude mice induced by ganciclovir treatment and all the tumors disappeared. The wild-type p53 transduced tumor cells became markedly susceptible to irradiation and anticancer agents. Administration of cisplatine noticeably suppressed the growth of p53 transduced tumors inoculated in nude mice. We established the clinical protocol of gene therapy for esophageal cancer using wild-type p53 gene with adenovirus vector. In this autumn we are going to start this clinical trial.
Insights
Gene therapy shows promise for esophageal cancer. Interleukin-2 (IL-2) or granulocyte-macrophage colony-stimulating factor (GM-CSF) genes reduced tumor formation. Suicide gene therapy with herpes simplex virus-thymidine kinase (HSV-tk) and p53 gene therapy also demonstrated significant antitumor effects.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Gene Therapy
Context:
- Esophageal cancer remains a significant health challenge with limited treatment options.
- Gene therapy offers a novel approach to target and eliminate cancer cells.
- This study investigates the efficacy of several gene-based strategies in preclinical models of esophageal cancer.
Purpose:
- To evaluate the antitumor effects of retrovirally expressed interleukin-2 (IL-2), granulocyte-macrophage colony-stimulating factor (GM-CSF), herpes simplex virus-thymidine kinase (HSV-tk), and p53 genes in human esophageal cancer cells.
- To assess the potential of these genetic modifications in combination with established treatments like ganciclovir, irradiation, and cisplatin.
- To lay the groundwork for a clinical trial using p53 gene therapy for esophageal cancer.
Summary:
- Retroviral expression of IL-2 or GM-CSF in esophageal cancer cells led to a loss of tumorigenicity and demonstrated antitumor effects when injected into existing tumors.
- Suicide gene therapy using HSV-tk, followed by ganciclovir treatment, resulted in complete tumor disappearance in nude mice.
- Transduction with wild-type p53 gene sensitized esophageal cancer cells to irradiation and chemotherapy (cisplatin), significantly suppressing tumor growth.
- A clinical protocol for esophageal cancer gene therapy utilizing wild-type p53 with an adenovirus vector has been established, with a trial set to commence.
Impact:
- These findings highlight the therapeutic potential of various gene-based strategies for esophageal cancer.
- The study provides a strong preclinical basis for advancing p53 gene therapy into clinical application.
- Successful gene therapy could lead to more effective and targeted treatments for esophageal cancer patients, improving outcomes and reducing side effects.