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Complete tumor prevention by engineered tumor cell vaccines employing nonviral vectors

Cancer Gene Therapy volume 10, pages 887–897 (2003)Cite this article

Abstract

We report that 100% mice survival after tumor challenge is achieved with cytokine-engineered cells employing nonviral lipoplexes and without using viral vectors. We describe this effect with cytokine-secreting tumor cell vaccines, based on cell clones or fresh transfected cells. Tumor cells were transfected with murine granulocyte–macrophage colony-stimulating factor (GM-CSF) or IL-4 plasmids employing the cationic lipid DOTAP, were irradiated (150 Gy) and kept frozen until use. The transfection efficacy was analyzed by qRT-PCR and flow cytometry. Vaccination induced potent antitumor rejection, resulting in 100% mice survival. Furthermore, the antitumor immunity was long lasting, since a two-fold survival delay was observed in mice after tumor rechallenge (6 months later). While cell clones secreting GM-CSF were the most effective in wild-type tumor cell rejection, little or no effect was observed with clones secreting IL-4. We found similar antitumor efficacy employing fresh transfected cells by nonviral procedures, demonstrating that cells genetically modified by nonviral vectors (both clones and fresh transfected cells) are a safe and efficient tool for antitumor vaccines. These vaccines allow us to achieve the highest antitumor efficacy based on nonviral gene therapy techniques. In addition, the vaccination success with fresh transfected cells simplifies the procedure and provides new insights into the clinical application of nonviral gene therapy procedures.

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Acknowledgements

We thank all those who have collaborated in the present study, particularly Dr Rosa Algàs and Dr Diego Dualde from the Service of Radiotherapy (University Clinic Hospital, Valencia, Spain) for their help and kindness, and our colleagues Vicent Guillem and Isaias Sanmartín for their collaboration in preparing the vaccines and in the in vivo administration. The plasmids employed were kindly donated by Dr Andrés Koenig (MOLOGEN, Germany). The present work has been supported by the Generalitat Valenciana, IMPIVA.

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Authors and Affiliations

  1. Departamento de Farmacología, Grupo de Terapia Génica, Facultad de Medicina, Universitat de València, Avda de Blasco Ibáñez no. 15, Valencia, 46010, Spain

    Inés Moret-Tatay, Antonio Crespo & Salvador F Aliño

  2. ASAC Pharmaceutical International AIE Alicante, Spain

    Joaquín Díaz & Francisco M Marco

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  1. Inés Moret-Tatay
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Correspondence to Salvador F Aliño.

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Moret-Tatay, I., Díaz, J., Marco, F. et al. Complete tumor prevention by engineered tumor cell vaccines employing nonviral vectors. Cancer Gene Ther 10, 887–897 (2003). https://doi.org/10.1038/sj.cgt.7700646

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