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Sindbis viral vectors target hematopoietic malignant cells

Cancer Gene Therapy volume 19, pages 757–766 (2012)Cite this article

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Abstract

Sindbis viral vectors target and inhibit the growth of various solid tumors in mouse models. However, their efficacy against blood cancer has not been well established. Here, we show that Sindbis vectors infect and efficiently trigger apoptosis in mouse BW5147 malignant hematopoietic T-cells, but only at low levels in human lymphoma and leukemia cells (Jurkat, Karpas, CEM, DHL and JB). The Mr 37/67 kD laminin receptor (LAMR) has been suggested to be the receptor for Sindbis virus. However, JB cells, which are infected by Sindbis at low efficiency, express high levels of LAMR, revealing that additional factors are involved in Sindbis tropism. To test the infectivity and therapeutic efficacy of Sindbis vectors against malignant hematopoietic cells in vivo, we injected BW5147 cells intraperitoneally into (C3HXAKR) F1 hybrid mice. We found that Sindbis vectors targeted the tumors and significantly prolonged survival of tumor-bearing mice. We also tested the Sindbis vectors in a transgenic CD4-Rgr model, which spontaneously develop thymic lymphomas. However, infectivity in this model was less efficient. Taken together, these results demonstrate that Sindbis vectors have the potential to target and kill hematopoietic malignancies in mice, but further research is needed to evaluate the mechanism underlining the susceptibility of human lymphoid malignancies to Sindbis therapy.

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Acknowledgements

We thank Dr Tomer Granot and Ms Susanne Tranguch for the critical reading of the manuscript and helpful discussions. This study was supported by NIH CA50434 and Lymphoma & Leukemia Society 6064-07 grants. All animal experiments were performed in both the animal facility of NYU Langone Medical Center and of the Joan and Joel Smilow research center according to the NIH guidelines (Guide for the care and use of the Laboratory Animals, 1996).

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  1. J-C Tseng

    Present address: 2Present address: Dana-Farber Cancer Institute, Boston, MA, USA,

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  1. Department of Pathology and NYU Cancer Institute, New York University School of Medicine, New York, NY, USA

    R Suzme, J-C Tseng, B Levin, S Ibrahim, D Meruelo & A Pellicer

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Suzme, R., Tseng, JC., Levin, B. et al. Sindbis viral vectors target hematopoietic malignant cells. Cancer Gene Ther 19, 757–766 (2012). https://doi.org/10.1038/cgt.2012.56

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