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Oncolytic virotherapy of breast cancer.

by Jennifer C Hu, Matthew J Booth, Gopichand Tripuraneni, Derek Davies, Syed a a Zaidi, Manuela Tamburo de Bella, Martin J Slade, Stephen B Marley, Myrtle Y a Gordon, Robert S Coffin, R Charles Coombes, Tahereh Kamalati, M Hawke, M C Jaberoo, R E Stead, V M Reddy, E Haff, S J Platt, P Rawlins, C D Drews, A B Dilley, A D Athukorala, M U Devi, E Joshua, K Kirankumar, C M Thirukkumaran, J M Luider, D a Stewart, T Alain, J a Russell, I a Auer, P Forsyth, D G Morris, M Toda, R L Martuza, Samuel D Rabkin, Zebin Hu, Helen Gerseny, Zhenwei Zhiling Zhang, Yun-Ju Chen, Arthur Berg, Stuart Stock, Prem Seth, M Gil, M Bieniasz, M Seshadri, D Fisher, M J Ciesielski, R K Pandey, D Kozbor, D Wodarz, Darren R Shafren, D J Dorahy, R a Ingham, G F Burns, Richard D Barry, Andreas D Hartkopf, Tanja Fehm, Diethelm Wallwiener, Ulrich M Lauer, Renbin Liu, Susan Varghese, S V T-antigen Transgenic, Caroline J Breitbach, Jennifer M Paterson, Chantal G Lemay, Theresa J Falls, Allison McGuire, Kelley a Parato, David F Stojdl, Manijeh Daneshmand, Kelly Speth, David Kirn, J Andrea McCart, Harold Atkins, John C Bell, Elizabeth J Kelly, Elizabeth M Hadac, Suzanne Greiner, Stephen J Russell, Timothy P Cripe, Pin-Yi Wang, Paola Marcato, Yonatan Y Mahller, Patrick Wk Lee, Allied Health Source, Laura Menotti, Giordano Nicoletti, Valentina Gatta, Stefania Croci, Lorena Landuzzi, Carla De Giovanni, Patrizia Nanni, Pier-Luigi Lollini, Gabriella Campadelli-Fiume, M Bazan-Peregrino, R C a Sainson, R C Carlisle, C Thoma, R a Waters, C Arvanitis, a L Harris, R Hernandez-Alcoceba, L W Seymour, Gough G Au, Tam Nguyen, Nicole G Newcombe, Erin S Haley, Leone G Beagley, E Susanne Johansson, Peter Hersey, Timothy Kottke, Geoff Hall, Jose Pulido, Rosa Maria Diaz, Jill Thompson, Heung Chong, Peter Selby, Matt Coffey, Hardev Pandha, John Chester, Alan Melcher, Kevin Harrington, Richard Vile, C M Seubert, J Stritzker, M Hess, U Donat, J B Sturm, N Chen, J M von Hof, B Krewer, L F Tietze, I Gentschev, a a Szalay, Paul Gregorevic, Michael J Blankinship, James M Allen, Robert W Crawford, Daniel G Miller, David W Russell, Jeffrey S Chamberlain, Lisa F Lincz, Arno Enno show all authors
Molecular therapy : the journal of the American Society of Gene Therapy ()

Abstract

Autologous hematological stem cell transplantation (ASCT) is used for the treatment of many hematological and several solid cancers. ASCT, however, has proven disappointing as a therapeutic strategy for breast cancer. Our group and others have previously shown that breast cancer micrometastases found in patients' apheresis products (APs) predict shorter progression-free and overall survival. The implications of this finding are twofold: (i) contaminating tumor cells (CTCs) in AP reflect a higher systemic disease burden and/or (ii) reinfused CTCs contribute to relapse/progressive disease. To date, purging strategies have been disappointing. We have previously demonstrated the oncolytic properties of reovirus in in vitro, in vivo and ex vivo systems. In the present study, we tested the hypothesis that reovirus purges CTCs in a breast cancer cell line purging model. Reovirus-infected human breast cancer cell lines (HTB 133, HTB 132, SKBR3 and MCF7) exhibited cell death within days. Admixtures of AP with cells from breast tumor cell lines, which were then exposed to reovirus, showed complete purging of CTCs (assessed via flow cytometry/tumor cell outgrowth analysis) without deleterious effect on CD34+ cells. Our results provide preclinical support for the ex vivo use of reovirus as a purging modality for breast cancer during ASCT.

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