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Treatment of pulmonary metastatic tumors in mice using lentiviral vector-engineered stem cells

Cancer Gene Therapy volume 15, pages 73–84 (2008)Cite this article

Abstract

Active cancer immunotherapy relies on functional tumor-specific effector T lymphocytes for tumor elimination. Dendritic cells (DCs), as most potent antigen-presenting cells, have been popularly employed in clinical and experimental tumor treatments. We have previously demonstrated that lentiviral vector-mediated transgene delivery to DC progenitors, including bone marrow cells and hematopoietic stem cells, followed by transplantation supports systemic generation of great numbers of tumor antigen-presenting DCs. These DCs subsequently stimulate marked and systemic immune activation. Here, we examined whether this level of immune activation is sufficient to overcome tumor-induced tolerogenic environment for treating an established aggressive epithelial tumor. We showed that a combination treatment of granulocyte macrophage-colony stimulating factor and cytosine-phosphate-guanine-containing oligonucleotide stimulated large numbers of tumor antigen-presenting DCs in situ from transgene-modified stem cells. Moreover, these in situ generated and activated DCs markedly stimulated activation of antigen-specific CD4 and CD8 T cells by augmenting their numbers, as well as function, even in a tumor-bearing tolerogenic environment. This leads to significant improvement in the therapeutic efficacy of established pulmonary metastases. This study suggests that lentiviral vector-modified stem cells as DC progenitors may be used as an effective therapeutic regimen for treating metastatic epithelial tumors.

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Acknowledgements

We thank Ms Jennifer Aguirre and Jennifer Simkin for technical assistance in immunohistochemistry staining and image acquisition. This research was supported by funds from Louisiana Gene Therapy Consortium, Stanley S Scott Cancer Center and grants from the Susan Komen Breast Cancer Foundation and National Institutes of Health to YC (CA112065 and P20RR021970). Gina Washington was supported by an NCI summer student scholarship.

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  1. X Zhang and P Zhao: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, LA, USA

    X Zhang, P Zhao, C Kennedy, J Wiegand, G Washington, L Marrero & Y Cui

  2. Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA

    K Chen, J Wiegand, L Marrero & Y Cui

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  1. X Zhang
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  2. P Zhao
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Correspondence to Y Cui.

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Zhang, X., Zhao, P., Kennedy, C. et al. Treatment of pulmonary metastatic tumors in mice using lentiviral vector-engineered stem cells. Cancer Gene Ther 15, 73–84 (2008). https://doi.org/10.1038/sj.cgt.7701108

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