title: A vaccine targeting angiomotin induces an antibody response which alters tumor vessel permeability and hampers the growth of established tumors.
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.
authors.affiliation: Molecular Biotechnology Center, University of Turin, Turin, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Arigoni
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Barutello
authors.forename: Stefania
authors.initials: S
authors.lastname: Lanzardo
authors.forename: Dario
authors.initials: D
authors.lastname: Longo
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.forename: Claudia
authors.initials: C
authors.lastname: Curcio
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Irmeli
authors.initials: I
authors.lastname: Barkefors
authors.forename: Lars
authors.initials: L
authors.lastname: Holmgren
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
mesh_terms: D000091082:Angiomotins; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D002199:Capillary Permeability / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D007108:Immune Tolerance; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051381:Rats; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
chemical_list: C511047:Amot protein, mouse; D000091082:Angiomotins; D019496:Cancer Vaccines; D036341:Intercellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D019444:Vaccines, DNA