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SV40 Pseudovirion gene delivery of a toxin to treat human adenocarcinomas in mice

Cancer Gene Therapy volume 13, pages 648–657 (2006)Cite this article

Abstract

SV40 vectors packaged in vitro (pseudovirions) are an efficient delivery system for plasmids up to 17.7 kb, with or without SV40 sequences. A truncated Pseudomonas exotoxin gene (PE38) was delivered into various human cells (HeLa, KB-3-1, human lymphoblastoids, and erythroleukemia cells), in vitro using pseudovirions. The number of viable cells was reduced significantly in the PE38-transduced cells. Human KB adenocarcinomas growing in mice were treated with intratumoral injection of PE38 packaged in vitro, and tumor size decreased significantly. Intraperitoneal treatments were as effective in reducing tumor size as intratumoral treatments. To check the viability of mock- or PE38-treated mice, every 4 days they were weighed, their blood was tested, and various tissues were screened for pathology. All parameters showed that the in vitro-packaged vectors, injected into tumors or intraperitoneally, caused no abnormalities in mice. The combined treatment of doxorubicin with in vitro-packaged PE38 reduced tumor size slightly more than each of the treatments separately. However, the combined treatment did not cause the weight loss seen with doxorubicin alone. These results indicate that SV40 in vitro packaging is an effective system for cancer gene delivery using two different routes of injection and in combination with chemotherapy.

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Acknowledgements

This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. We thank Ariella Oppenheim (The Hebrew University, Hadassah Medical School and Hadassah University Hospital, Jerusalem, Israel) for fruitful collaboration on the SV40 vectors, and Ira Pastan, LMB, NIH for productive discussions. We thank Georgina F Miller and Michael Eckhaus, ORS/DIRS/VRP, NIH, for providing us with pathological reports and blood tests results, and George Leiman for insightful editorial assistance.

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  1. C Kimchi-Sarfaty

    Present address: Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, 20892, USA

Authors and Affiliations

  1. Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    C Kimchi-Sarfaty, W D Vieira, D Dodds, A Sherman, S Shinar & M M Gottesman

  2. Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    R J Kreitman

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  1. C Kimchi-Sarfaty
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Correspondence to M M Gottesman.

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Kimchi-Sarfaty, C., Vieira, W., Dodds, D. et al. SV40 Pseudovirion gene delivery of a toxin to treat human adenocarcinomas in mice. Cancer Gene Ther 13, 648–657 (2006). https://doi.org/10.1038/sj.cgt.7700943

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