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Immunotherapy with bovine aortic endothelial cells in subcutaneous and intracerebral glioma models in rats: effects on survival time, tumor growth, and tumor neovascularization

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Abstract

High-grade gliomas are aggressive tumors of the central nervous system characterized by endothelial cell proliferation and a high degree of vascularity. Conventional antitumoral treatments (i.e., surgery, radiotherapy, and chemotherapy) do not achieve satisfactory results (median survival in glioblastoma 12–18 months). It has been suggested that immunotherapy with xenogenic endothelial cells could slow tumor growth rate in a number of tumors in a murine model, but the study did not include gliomas. In experiments performed in our laboratory, vaccination with proliferating bovine aortic endothelium increased survival time in Fischer rats inoculated intracerebrally with 9L. Immunotherapy was also able to reduce the growth of subcutaneously injected 9L gliosarcoma cells in Fischer rats and to decrease microvessel density within the tumors, in the absence of major organ toxicity. Immunoglobulins (Ig) in the sera from vaccinated rats stained bovine aortic endothelium as well as human umbilical vein endothelium in active proliferation. Moreover, immune sera from immunized rats stained microvessels of human malignant glioma specimens and vessels of intracerebrally implanted tumors. Two proteins of MW of 11 and 19 kDa were identified by Western blot as targets of Ig elicited by vaccination. A possible future development is to select peptides/proteins suitable for vaccination in humans, avoiding the biohazards connected with xenogenic whole-cell vaccination.

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Acknowledgements

We would like to thank Dr Bianca Pollo for kindly providing sections of human glioblastomas, Dr Laura Cajola for helpful discussions about histochemical analysis, and Dr Luisa Bozzo for collaboration in Western blot analysis.

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Authors and Affiliations

  1. Department of Neurooncology, Istituto Nazionale Neurologico “C. Besta”, 20133, Milan, Italy

    E. Corsini, M. Gelati, C. Calatozzolo, G. Alessandri, S. Frigerio, E. Parati, D. Croci, A. Boiardi & A. Salmaggi

  2. Istituto di Microbiologia, Università degli Studi di Brescia—Spedali Civili, Brescia, Italy

    M. De Francesco & C. Poiesi

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  1. E. Corsini
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  2. M. Gelati
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  3. C. Calatozzolo
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  4. G. Alessandri
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  5. S. Frigerio
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  6. M. De Francesco
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  7. C. Poiesi
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  8. E. Parati
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  9. D. Croci
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  10. A. Boiardi
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  11. A. Salmaggi
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Correspondence to A. Salmaggi.

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Corsini, E., Gelati, M., Calatozzolo, C. et al. Immunotherapy with bovine aortic endothelial cells in subcutaneous and intracerebral glioma models in rats: effects on survival time, tumor growth, and tumor neovascularization. Cancer Immunol Immunother 53, 955–962 (2004). https://doi.org/10.1007/s00262-004-0529-5

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  • DOI: https://doi.org/10.1007/s00262-004-0529-5

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