Original Paper

Angiogenesis

, Volume 15, Issue 2, pp 305-316

Open Access This content is freely available online to anyone, anywhere at any time.

A vaccine targeting angiomotin induces an antibody response which alters tumor vessel permeability and hampers the growth of established tumors

  • Maddalena ArigoniAffiliated withMolecular Biotechnology Center, University of Turin
  • , Giuseppina BarutelloAffiliated withMolecular Biotechnology Center, University of Turin
  • , Stefania LanzardoAffiliated withMolecular Biotechnology Center, University of Turin
  • , Dario LongoAffiliated withMolecular Imaging Center, Department of Chemistry IFM, University of Turin
  • , Silvio AimeAffiliated withMolecular Imaging Center, Department of Chemistry IFM, University of Turin
  • , Claudia CurcioAffiliated withAging Research Center, “Gabriele d’Annunzio” University Foundation
  • , Manuela IezziAffiliated withAging Research Center, “Gabriele d’Annunzio” University Foundation
  • , Yujuan ZhengAffiliated withDepartment of Oncology and Pathology, Cancer Centre Karolinska, Karolinska Institutet
  • , Irmeli BarkeforsAffiliated withDepartment of Oncology and Pathology, Cancer Centre Karolinska, Karolinska Institutet
    • , Lars HolmgrenAffiliated withDepartment of Oncology and Pathology, Cancer Centre Karolinska, Karolinska Institutet
    • , Federica CavalloAffiliated withMolecular Biotechnology Center, University of TurinMolecular Biotechnology Center Email author 

Abstract

Angiomotin (Amot) is one of several identified angiostatin receptors expressed by the endothelia of angiogenic tissues. We have shown that a DNA vaccine targeting Amot overcome immune tolerance and induce an antibody response that hampers the progression of incipient tumors. Following our observation of increased Amot expression on tumor endothelia concomitant with the progression from pre-neoplastic lesions to full-fledged carcinoma, we evaluated the effect of anti-Amot vaccination on clinically evident tumors. Electroporation of plasmid coding for the human Amot (pAmot) significantly delayed the progression both of autochthonous tumors in cancer prone BALB-neuT and PyMT genetically engineered mice and transplantable TUBO tumor in wild-type BALB/c mice. The intensity of the inhibition directly correlated with the titer of anti-Amot antibodies induced by the vaccine. Tumor inhibition was associated with an increase of vessels diameter with the formation of lacunar spaces, increase in vessel permeability, massive tumor perivascular necrosis and an effective epitope spreading that induces an immune response against other tumor associated antigens. Greater tumor vessel permeability also markedly enhances the antitumor effect of doxorubicin. These data provide a rationale for the development of novel anticancer treatments based on anti-Amot vaccination in conjunction with chemotherapy regimens.

Keywords

Angiomotin DNA vaccination Vessel permeability Antibodies Chemotherapy