Immunotherapy Of Cancer With Tumor Cell Vaccine Based On The Chicken Homologous Matrix Metalloproteinase-2

matrix metalloproteinase-2 (MMP-2), a 72kD gelatine A, plays an important role in the processes involving degradation of the extracellular matrix (ECM).Matrix metalloproteinase-2 (MMP-2) is overexpressed in human cancers and facilitates tumor growth and metastasis. Breaking of immune tolerance of MMP-2 should be a useful approach to cancer therapy by active immunity. To demonstrate the feasibility, we used transfectants with plasmid DNA encoding chicken homologous MMP-2 or corresponding mouse MMP-2 to evaluate tumor cells with MMP-2 as a tumor vaccine. Autoantibodies against mouse MMP-2 were identified by Western blot analysis and ELISA. The anti-tumor activity and production of autoantibodies against MMP-2 could be abrogated by depletion of CD4+ T lymphocytes. The CD8+-dependent MHC I restricted CTL response to MMP-2 positive tumor cells was also observed. All the induced antibody and cellular immune responses could cross-react with MMP-2 from mice or chichen. In addition, antitumor activity acquired with adoptive purified antibody and CD8+ T lymphocytes. We found that immunotherapy with c-MMP-2 was effective at both cellular and humoral antitumor immunity in several tumor models in mice. Taken together, these findings suggested the antitumor immunity induced by chicken MMP-2 may be provoked in a cross-reaction between the xenogeneic homologous and self-mmp-2, and may provide insight into treatment of MMP-2-positive tumors through the induction of the autoimmune response against MMP-2. Theobservations may provide a vaccine strategy for cancer therapy through the induction of autoimmunity and CTL in a cross reaction with transfectants.