Gene therapy using anticancer drug-resistance genes

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Myelosuppression is a major dose-limiting factor in cancer chemotherapy. Introduction of drug-resistance genes into bone marrow cells of cancer patients has been proposed to overcome this limitation. In theory, any gene whose expression protects cells against the toxic effects of chemotherapy should be useful in vivo for this purpose. Among such genes, human multidrug-resistance gene (MDR1) and O6-methylguanine DNA methyltransferase gene (MGMT) have been studied most extensively for this purpose, and clinical trials of drug-resistance gene therapy have been started in the US for cancer patients who undergo high-dose chemotherapy with autologous hematopoietic stem cell transplantation. In Japan, our clinical protocol of MDR1 gene therapy, "A clinical study of drug-resistance gene therapy to improve the efficacy and safety of chemotherapy against breast cancer", has been approved by our IRB and submitted to the government. To improve the efficacy and safety of this drug-resistance gene therapy, we have constructed a series of MDR1-bicistronic retrovirus vectors using a retrovirus backbone of Harvey murine sarcoma virus and internal ribosome entry site (IRES) from picornavirus to coexpress a second gene with the MDR1 gene. MDR1-MGMT bicistronic vectors can be used to protect bone marrow cells of cancer patients from combination chemotherapy with MDR1-related anticancer agents and nitrosoureas. In addition, MDR1-bicistronic retrovirus vectors can be designed to use the MDR1 gene as an in vivo selectable marker to enrich the transduced cells which express therapeutic genes, if disease is curable by the expression of a single-peptide gene in bone marrow cells or any types of peripheral blood cells.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalGan to kagaku ryoho. Cancer & chemotherapy
Volume26
Issue number1
Publication statusPublished - 1999 Jan
Externally publishedYes

Fingerprint

Drug Resistance
Genetic Therapy
Genes
Retroviridae
Bone Marrow Cells
Drug Therapy
Methyltransferases
Harvey murine sarcoma virus
Neoplasms
Picornaviridae
MDR Genes
Safety
Poisons
Research Ethics Committees
Hematopoietic Stem Cell Transplantation
DNA
Clinical Protocols
Combination Drug Therapy
Antineoplastic Agents
Blood Cells

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology

Cite this

Gene therapy using anticancer drug-resistance genes. / Sugimoto, Yoshikazu.

In: Gan to kagaku ryoho. Cancer & chemotherapy, Vol. 26, No. 1, 01.1999, p. 1-9.

Research output: Contribution to journalArticle

@article{85a9b7b014eb41e69f546e4c5c831b98,
title = "Gene therapy using anticancer drug-resistance genes",
abstract = "Myelosuppression is a major dose-limiting factor in cancer chemotherapy. Introduction of drug-resistance genes into bone marrow cells of cancer patients has been proposed to overcome this limitation. In theory, any gene whose expression protects cells against the toxic effects of chemotherapy should be useful in vivo for this purpose. Among such genes, human multidrug-resistance gene (MDR1) and O6-methylguanine DNA methyltransferase gene (MGMT) have been studied most extensively for this purpose, and clinical trials of drug-resistance gene therapy have been started in the US for cancer patients who undergo high-dose chemotherapy with autologous hematopoietic stem cell transplantation. In Japan, our clinical protocol of MDR1 gene therapy, {"}A clinical study of drug-resistance gene therapy to improve the efficacy and safety of chemotherapy against breast cancer{"}, has been approved by our IRB and submitted to the government. To improve the efficacy and safety of this drug-resistance gene therapy, we have constructed a series of MDR1-bicistronic retrovirus vectors using a retrovirus backbone of Harvey murine sarcoma virus and internal ribosome entry site (IRES) from picornavirus to coexpress a second gene with the MDR1 gene. MDR1-MGMT bicistronic vectors can be used to protect bone marrow cells of cancer patients from combination chemotherapy with MDR1-related anticancer agents and nitrosoureas. In addition, MDR1-bicistronic retrovirus vectors can be designed to use the MDR1 gene as an in vivo selectable marker to enrich the transduced cells which express therapeutic genes, if disease is curable by the expression of a single-peptide gene in bone marrow cells or any types of peripheral blood cells.",
author = "Yoshikazu Sugimoto",
year = "1999",
month = "1",
language = "English",
volume = "26",
pages = "1--9",
journal = "Japanese Journal of Cancer and Chemotherapy",
issn = "0385-0684",
publisher = "Japanese Journal of Cancer and Chemotherapy Publishers Inc.",
number = "1",

}

TY - JOUR

T1 - Gene therapy using anticancer drug-resistance genes

AU - Sugimoto, Yoshikazu

PY - 1999/1

Y1 - 1999/1

N2 - Myelosuppression is a major dose-limiting factor in cancer chemotherapy. Introduction of drug-resistance genes into bone marrow cells of cancer patients has been proposed to overcome this limitation. In theory, any gene whose expression protects cells against the toxic effects of chemotherapy should be useful in vivo for this purpose. Among such genes, human multidrug-resistance gene (MDR1) and O6-methylguanine DNA methyltransferase gene (MGMT) have been studied most extensively for this purpose, and clinical trials of drug-resistance gene therapy have been started in the US for cancer patients who undergo high-dose chemotherapy with autologous hematopoietic stem cell transplantation. In Japan, our clinical protocol of MDR1 gene therapy, "A clinical study of drug-resistance gene therapy to improve the efficacy and safety of chemotherapy against breast cancer", has been approved by our IRB and submitted to the government. To improve the efficacy and safety of this drug-resistance gene therapy, we have constructed a series of MDR1-bicistronic retrovirus vectors using a retrovirus backbone of Harvey murine sarcoma virus and internal ribosome entry site (IRES) from picornavirus to coexpress a second gene with the MDR1 gene. MDR1-MGMT bicistronic vectors can be used to protect bone marrow cells of cancer patients from combination chemotherapy with MDR1-related anticancer agents and nitrosoureas. In addition, MDR1-bicistronic retrovirus vectors can be designed to use the MDR1 gene as an in vivo selectable marker to enrich the transduced cells which express therapeutic genes, if disease is curable by the expression of a single-peptide gene in bone marrow cells or any types of peripheral blood cells.

AB - Myelosuppression is a major dose-limiting factor in cancer chemotherapy. Introduction of drug-resistance genes into bone marrow cells of cancer patients has been proposed to overcome this limitation. In theory, any gene whose expression protects cells against the toxic effects of chemotherapy should be useful in vivo for this purpose. Among such genes, human multidrug-resistance gene (MDR1) and O6-methylguanine DNA methyltransferase gene (MGMT) have been studied most extensively for this purpose, and clinical trials of drug-resistance gene therapy have been started in the US for cancer patients who undergo high-dose chemotherapy with autologous hematopoietic stem cell transplantation. In Japan, our clinical protocol of MDR1 gene therapy, "A clinical study of drug-resistance gene therapy to improve the efficacy and safety of chemotherapy against breast cancer", has been approved by our IRB and submitted to the government. To improve the efficacy and safety of this drug-resistance gene therapy, we have constructed a series of MDR1-bicistronic retrovirus vectors using a retrovirus backbone of Harvey murine sarcoma virus and internal ribosome entry site (IRES) from picornavirus to coexpress a second gene with the MDR1 gene. MDR1-MGMT bicistronic vectors can be used to protect bone marrow cells of cancer patients from combination chemotherapy with MDR1-related anticancer agents and nitrosoureas. In addition, MDR1-bicistronic retrovirus vectors can be designed to use the MDR1 gene as an in vivo selectable marker to enrich the transduced cells which express therapeutic genes, if disease is curable by the expression of a single-peptide gene in bone marrow cells or any types of peripheral blood cells.

UR - http://www.scopus.com/inward/record.url?scp=0032605180&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032605180&partnerID=8YFLogxK

M3 - Article

C2 - 9987494

AN - SCOPUS:0032605180

VL - 26

SP - 1

EP - 9

JO - Japanese Journal of Cancer and Chemotherapy

JF - Japanese Journal of Cancer and Chemotherapy

SN - 0385-0684

IS - 1

ER -