Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells

Nat. Med. 11, 1073-1081 (2005)

Speaker: 張家綸                                          Time: 14:10~15:00, Nov. 23, 2005

Commentator: 蕭璦莉 老師                    Place: Room 601

Abstract

Gene therapy is a potential approach in the treatment of cancer. Systemic delivery of genes to tumors in a fully immunocompetent setting, however, is problematic because of vector neutralization and nonspecific adhesion ¹. The authors utilized the retroviral particles encoding therapeutic genes to “hitchhike” to the surfaces of antigen-specific T cell ², and subsequently the viruses were released to the tumor site after in vivo transferring the T-cell into the immunocompetent host. Antigen-specific T cells of mouse origin treated with trypsin or heparanase can cleave heparan sulfate glycosaminoglycans and showed hand-off effects. Interestingly, metastatic cells and active T cells often express heparanase, thus the authors suggest that malignant phenotype and T-cell activation could enhance viral hand off. Their data demonstrated that adoptive transfer of antigen-specific T cells loaded with viruses encoding interleukin (IL)-12 or Herpes Simplex Virus thymidine kinase enhanced immunotherapy against the metastatic disease as compared to adoptive T cell transfer alone. All together, this approach provides us an alternative method to deliver therapeutic viral vectors with the help of antigen-specific T cells.

References

1.          Vile, R.G., Russell, S.J. & Lemoine, N.R. Cancer gene therapy: hard lessons and new courses. Gene Ther. 7, 2–8 (2000).

2.          Pizzato, M. et al. Evidence for nonspecific adsorption of targeted retrovirus vector particles to cells. Gene Ther. 8, 1088–1096 (2001).