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Comparative antitumor effect among GM-CSF, IL-12 and GM-CSF+IL-12 genetically modified tumor cell vaccines

Cancer Gene Therapy volume 20, pages 576–581 (2013)Cite this article

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Abstract

Genetically modified cells have been shown to be one of the most effective cancer vaccine strategies. An evaluation is made of the efficacy of both preventive and therapeutic antitumor vaccines against murine melanoma, using C57BL/6 mice and irradiated B16 tumor cells expressing granulocyte and macrophage colony-stimulating factor (GM-CSF), interleukin-12 (IL-12) or both. Tumor was transplanted by the injection of wild-type B16 cells. Tumor growth and survival were measured to evaluate the efficacy of vaccination. Specific humoral response and immunoglobulin G (IgG) switch were evaluated measuring total IgG and IgG1 and IgG2a subtypes against tumor membrane proteins of B16 cells. In preventive vaccination, all treated groups showed delayed tumor growth. In addition, the group vaccinated to express only GM-CSF achieved 100% animal survival (P<0.005). Vaccination with GM-CSF+IL-12-producing B16 cells yielded lesser results (60% survival, P<0.005). Furthermore, all surviving animals remained disease-free after second tumor implantation 1 year later. The therapeutic vaccination strategies resulted in significantly delayed tumor growth, mainly using B16 cells producing GM-CSF+IL-12 cytokines, with 70% tumor growth inhibition (P<0.001)—although none of the animals reached overall survival. The results obtained suggest that the GM-CSF+IL-12 combination only increases the efficacy of therapeutic vaccines. No differences in classical regulatory T cells were found among the different groups.

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Acknowledgements

This work was partially supported by FIS PI 021740 and SAF 2011-27002. We thank the central unit of research of the Faculty of Medicine of the University of Valencia for granted technical support.

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Author notes

  1. A Miguel and M J Herrero: These authors contributed equally to this work.

Authors and Affiliations

  1. Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain

    A Miguel, M J Herrero, L Sendra, M Sánchez & S F Aliño

  2. Instituto de Investigación Sanitaria La Fe, Valencia, Spain

    M J Herrero

  3. Servicio de Dermatología, Hospital Universitario La Fe, Valencia, Spain

    R Botella

  4. Departamento de Medicina, Facultad de Medicina, Universidad de Valencia, Valencia, Spain

    R Botella

  5. Servicio de Radioterapia, Hospital Clínico Universitario, Valencia, Spain

    R Algás

  6. Area Clínica del Medicamento, Unidad de Farmacología Clíınica, Hospital Universitario La Fe, Valencia, Spain

    S F Aliño

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  1. A Miguel
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Correspondence to M J Herrero or S F Aliño.

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Miguel, A., Herrero, M., Sendra, L. et al. Comparative antitumor effect among GM-CSF, IL-12 and GM-CSF+IL-12 genetically modified tumor cell vaccines. Cancer Gene Ther 20, 576–581 (2013). https://doi.org/10.1038/cgt.2013.54

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