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A vaccine targeting angiomotin induces an antibody response which alters tumor vessel permeability and hampers the growth of established tumors
- Source :
- Angiogenesis, Angiogenesis; Vol 15
- Publication Year :
- 2011
-
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. Electronic supplementary material The online version of this article (doi:10.1007/s10456-012-9263-3) contains supplementary material, which is available to authorized users.
- Subjects :
- Cancer Research
Angiogenesis
Physiology
Biomedicine general
Clinical Biochemistry
Cardiology
Vascular permeability
Biology
DNA vaccination
Cancer Vaccines
Angiomotin
Antibodies
Immune tolerance
Capillary Permeability
03 medical and health sciences
Mice
0302 clinical medicine
Immune system
Cell Line, Tumor
medicine
Immune Tolerance
Vaccines, DNA
Animals
Humans
Chemotherapy
Doxorubicin
030304 developmental biology
Vessel permeability
0303 health sciences
Mice, Inbred BALB C
Original Paper
Angiostatin
Neovascularization, Pathologic
Microfilament Proteins
Neoplasms, Experimental
Cell Biology
3. Good health
Rats
Biomedicine
Ophthalmology
Angiomotins
Oncology
030220 oncology & carcinogenesis
Immunology
Cancer research
Intercellular Signaling Peptides and Proteins
medicine.drug
Subjects
Details
- ISSN :
- 15737209
- Volume :
- 15
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Angiogenesis
- Accession number :
- edsair.doi.dedup.....171148a506c2a6ef3ff384128aa5255f