Cell-specific targeting of a thymidine kinase/ganciclovir gene therapy system using a recombinant sindbis virus vector

✍ Scribed by Yasushi Iijima; Kouichi Ohno; Hiroshi Ikeda; Keisuke Sawai; Brandi Levin; Daniel Meruelo

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 501 KB
• Volume: 80
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990105)80:1<110::aid-ijc21>3.0.co;2-8

✦ Synopsis

Transfer of the herpes simplex virus type 1 thymidine kinase (HSV-TK) gene into tumor cells using virus-based vectors in conjunction with ganciclovir (GCV) exposure provides a potential gene therapy strategy for the treatment of cancer. The possibility of using a novel targetable Sindbis virus expression vector containing the HSV-TK gene was examined. Baby hamster kidney (BHK) cells and several human tumor cells infected with a Sindbis virus containing the HSV-TK gene showed strong expression of HSV-TK protein. Cells transduced with the HSV-TK gene exhibited increased TK activity, ranging from 3-to 20-fold over an average baseline level. The human HeLa-CD4 ϩ cells infected with recombinant Sindbis virus containing the HSV-TK gene were sensitive to low concentrations of GCV (0.1-1 g/ml) and the 50% growth inhibitory concentration (IC 50 ) was 0.6 g/ml. We also demonstrated applications of cell typespecific Sindbis virus-mediated antigen-antibody targeting of the HSV-TK/GCV system in vitro. Sindbis virus containing the HSV-TK gene packaged in a helper virus displaying the IgGbinding domain of protein A on its envelope could infect various tumor cell lines in the presence of specific antibodies that recognize antigens on their surfaces. HSV-TK-transduced tumor cell lines exhibited sensitivity to GCV. Our data suggest the potential for targeted gene therapy of the HSV-TK/GCV system using a cell type-specific recombinant Sindbis virus vector-antibody system.