The breaking of immune tolerance against angiogenesis-associated molecules should be a useful approach for
cancer therapy by active immunity. We used chicken
integrin beta3 as a model
antigen to explore the feasibility of immunogene
therapy of the
tumors with a
vaccine based on a single xenogeneic homologous gene, targeting the molecules associated with angiogenesis. To test this concept we constructed a plasmid
DNA encoding the
ligand-binding domain of chicken
integrin beta3 (P-BD-C) and control vectors. We found that immunogene
therapy of
tumors with a
vaccine based on the
ligand-binding domain of chicken
integrin beta3 (P-BD-C) was effective in both protective and therapeutic anti-
tumor immunity in several
tumor models in mice.
Autoantibodies against
integrin beta3 in sera of mice immunized with the
ligand-binding domain of chicken
integrin beta3 could be found by Western blot analysis and ELISA assay. The purified
immunoglobulins were effective in the inhibition of endothelial cell proliferation in vitro, and in anti-
tumor activity as well as in the inhibition of angiogenesis by adoptive transfer in vivo. The anti-
tumor activity and the production of
integrin beta3-specific
autoantibodies (manifested by significantly elevated Ig G1 and Ig G2b) could be abrogated by the depletion of CD4+ T lymphocytes. These observations may provide a
vaccine strategy for
cancer therapy through the induction of the autoimmunity against the molecules associated with
tumor growth in a cross-reaction with a 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.