PMID- 14647305 OWN - NLM STAT- MEDLINE DCOM- 20040805 LR - 20201212 IS - 1087-0156 (Print) IS - 1087-0156 (Linking) VI - 22 IP - 1 DP - 2004 Jan TI - Systemic tumor targeting and killing by Sindbis viral vectors. PG - 70-7 AB - 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. FAU - Tseng, Jen-Chieh AU - Tseng JC AD - New York University Gene Therapy Center, NYU Cancer Institute, NYU School of Medicine, 550 First Avenue, New York, New York 10016, USA. FAU - Levin, Brandi AU - Levin B FAU - Hurtado, Alicia AU - Hurtado A FAU - Yee, Herman AU - Yee H FAU - Perez de Castro, Ignacio AU - Perez de Castro I FAU - Jimenez, Maria AU - Jimenez M FAU - Shamamian, Peter AU - Shamamian P FAU - Jin, Ruzhong AU - Jin R FAU - Novick, Richard P AU - Novick RP FAU - Pellicer, Angel AU - Pellicer A FAU - Meruelo, Daniel AU - Meruelo D LA - eng GR - CA22247/CA/NCI NIH HHS/United States GR - CA68498/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. DEP - 20031130 PL - United States TA - Nat Biotechnol JT - Nature biotechnology JID - 9604648 RN - EC 1.13.12.- (Luciferases) SB - IM MH - Animals MH - Cell Line MH - Female MH - Genetic Therapy/*methods MH - Genetic Vectors MH - Immunohistochemistry MH - Luciferases/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, SCID MH - Neoplasm Metastasis MH - Neoplasm Transplantation MH - Neoplasms/*therapy MH - Sindbis Virus/*genetics MH - Time Factors EDAT- 2003/12/03 05:00 MHDA- 2004/08/06 05:00 CRDT- 2003/12/03 05:00 PHST- 2003/10/01 00:00 [received] PHST- 2003/10/29 00:00 [accepted] PHST- 2003/12/03 05:00 [pubmed] PHST- 2004/08/06 05:00 [medline] PHST- 2003/12/03 05:00 [entrez] AID - nbt917 [pii] AID - 10.1038/nbt917 [doi] PST - ppublish SO - Nat Biotechnol. 2004 Jan;22(1):70-7. doi: 10.1038/nbt917. Epub 2003 Nov 30.