Systemic tumor targeting and killing by Sindbis viral vectors.
Successful cancer gene therapy requires a vector that systemically and specifically targets tumor cells throughout the body. Although several vectors have been developed to express cytotoxic genes via tumor-specific promoters or to selectively replicate in tumor cells, most are taken up and expressed by just a few targeted tumor cells. By contrast, we show here that blood-borne Sindbis viral vectors systemically and specifically infect tumor cells. A single intraperitoneal treatment allows the vectors to target most tumor cells, as demonstrated by immunohistochemistry, without infecting normal cells. Further, Sindbis infection is sufficient to induce complete tumor regression. We demonstrate systemic vector targeting of tumors growing subcutaneously, intrapancreatically, intraperitoneally and in the lungs. The vectors can also target syngeneic and spontaneous tumors in immune-competent mice. We document the anti-tumor specificity of a vector that systemically targets and eradicates tumor cells throughout the body without adverse effects.
Tseng
Jen-Chieh
JC
New York University Gene Therapy Center, NYU Cancer Institute, NYU School of Medicine, 550 First Avenue, New York, New York 10016, USA.
Levin
Brandi
B
Hurtado
Alicia
A
Yee
Herman
H
Perez de Castro
Ignacio
I
Jimenez
Maria
M
Shamamian
Peter
P
Jin
Ruzhong
R
Novick
Richard P
RP
Pellicer
Angel
A
Meruelo
Daniel
D
D000818:Animals; D002460:Cell Line; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000628:therapy*; D012845:Sindbis Virus / Q000235:genetics*; D013997:Time Factors
D008156:Luciferases