[Future directions of gene therapy for lung cancer].
Failure to achieve sustained therapeutic responses with conventional medical therapies has presented a challenge to gene therapy as a new approach to lung cancer. We used an allo-major histocompatibility complex class I gene (H-2Kb), and a gene encoding the thymidine kinase of herpes simplex virus type (HSV1-TK) as a drug sensitivity gene. The H-2Kb gene-transfected clones of mouse tumor cells were rejected completely by syngeneic DBA/2 mice. Furthermore, the mice that had rejected the H-2Kb gene-transfected clone became immune to and rejected the parental mouse tumor cells. Transfer of the retroviral vector-mediated HSV1-TK gene led to ganciclovir-dependent cytotoxicity in human lung cancer cells both in vivo and in vitro. Although these findings may lead to gene therapy to control lung cancer, further study is needed to determine the proper gene for targeting distant tumor cells, and the cell-specific promoter/enhancer sequences that regulate the tumor cell-specific expression of the transduced gene.
Hasegawa
Y
Y
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Shimokata
K
K
D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008285:Major Histocompatibility Complex / Q000235:genetics; D051379:Mice; D012190:Retroviridae / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics
D013937:Thymidine Kinase