EMMPRIN vaccination: a novel strategy to inhibit tumor progression and metastasis
EMMPRIN is now recognized as a therapeutic target for the treatment of cancer and inflammatory diseases, as it is found over-expressed in many types of solid tumors and in inflamed tissues, and is associated with tumor progression, angiogenesis, invasiveness, and metastasis. To actively immunize mice against EMMPRIN, we synthesized the specific epitope we identified before as a multiple antigenic peptide (MAP), that is considered more stable and more immunogenic than a monomeric peptide.
In two subcutaneous mice tumor models, our specific MAP immunization reduced tumor growth (by ~50%-100%) in comparison to the control groups receiving adjuvant only or scrambled MAP sequence. In mice that received the immunization and completely regressed the already palpable tumors, additional challenges with tumor cells (either s.c. or i.v to produce lung metastases) did not establish tumors and the mice remained healthy, suggesting a long-term (up to 11 months) effect that protected mice from tumor recurrence. In additional two mice models, where tumor cells were injected i.v. and developed lung metastases, the epitope-specific MAP drastically reduced, or even completely inhibited formation of metastases, in comparison to the control scrambled-MAP injected group. Therefore, we believe that this epitope-specific MAP could be a highly-effective drug that reduces or completely eradicates tumors, and prevents metastases and recurrences. Additional applications (e.g. in autoimmune diseases such as RA) will also be explored.