In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 20 ( 2001-09-25), p. 11545-11550
Kurzfassung:
Overcoming immune tolerance of the growth factors associated with
tumor growth should be a useful approach to cancer therapy by active immunity. We used vascular endothelial growth factor (VEGF) as a model
antigen to explore the feasibility of the immunogene tumor therapy with a vaccine based on a single xenogeneic homologous gene, targeting the
growth factors associated with angiogenesis. To test this concept, we constructed a plasmid DNA encoding Xenopus homologous
VEGF (XVEGF-p) and control vectors. We found that immunogene tumor therapy with a vaccine based on XVEGF was effective at both protective
and therapeutic antitumor immunity in several tumor models in mice. VEGF-specific autoantibodies in sera of mice immunized with XVEGF-p
could be found in Western blotting analysis and ELISA assay. The purified immunoglobulins were effective at the inhibition of
VEGF-mediated endothelial cell proliferation in
vitro , and at antitumor activity and the inhibition of
angiogenesis by adoptive transfer in vivo . The elevation
of VEGF in the sera of the tumor-bearing mice could be abrogated with XVEGF-p immunization. The antitumor activity and production of
VEGF-specific autoantibodies, significantly elevated IgG1 and IgG2b, could be abrogated by the depletion of CD4 + T lymphocytes.
The observations may provide a vaccine strategy for cancer therapy through the induction of autoimmunity against the growth factors
associated with tumor growth in a cross reaction with single xenogeneic homologous gene and may be of importance in the further exploration of
the applications of other xenogeneic homologous genes identified in human and other animal genome sequence projects in cancer therapy.
Materialart:
Online-Ressource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.191112198
Sprache:
Englisch
Verlag:
Proceedings of the National Academy of Sciences
Publikationsdatum:
2001
ZDB Id:
209104-5
ZDB Id:
1461794-8
SSG:
11
SSG:
12
