[Gene therapy for cancer].
The strategies of gene therapy for cancer can be classified as: 1. regulation of oncogenes and anti-oncogenes, 2. immunogenetherapy, 3. support of chemotherapy, 4. suicide gene therapy, and 5. gene marking. The first one is the strategy to inhibit the expression of oncogenes by their antisenses or rhybozymes, or to introduce anti-oncogenes into those tumor cells with the inactivate effector cells (lymphocytes) by transducing cytokine genes, etc., followed by retransfering the gene-modified effector cells to patients (adoptive immunotherapy). The other one is to augment antigenicity of tumor cells. The immunogenetherapy method has been widely used for 70% of gene therapy of human cancer, because cells can be transduced ex vivo. The anti-tumor effects of human gene therapy using a GM-CSF gene by Muligan et al. or an IL-2 gene by Tahara and Lotze are expected. The third is the strategy to protect bone marrows from large dose of anti-cancer drug by transducing a multidrug resistance gene into those bone marrow cells or periphen blood stem cells, overcoming dose limiting of the drug. The fourth strategy is to transduce the herpes simplex virus thymidine kinase (KSV-TK) gene for activating the cytocydal prodrug (ganciclovir: GCV) into tumor cells in order to kill the tumor cells themselves following administration of GCV. At present, vectors most widely used for gene transduction are retroviruses and adenoviruses. However, the transduction using these vectors are primarily conducted ex vivo. The direct in vivo gene delivery method to target tumor cells are required.
Sakamaki
S
S
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Niitsu
Y
Y
D016207:Cytokines / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D016376:Oligonucleotides, Antisense; D009857:Oncogenes; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase / Q000235:genetics
D016207:Cytokines; D016376:Oligonucleotides, Antisense; D013937:Thymidine Kinase