Discovery and immunologic validation of new antigens for therapeutic cancer vaccines.

Immunotherapy using both active and passive approaches is increasingly being used as a modality to treat human cancer. The last decade has seen a tremendous burst of activity in antigen discovery in cancer, and many new targets have now been identified for both monoclonal antibody therapy and active immunization. In addition, advances have been made in our understanding of the immune response against cancer and how new vaccine vectors, such as poxviruses, alphaviruses and bacterial vectors, can be used to overcome some of the traditional hurdles (e.g. self-tolerance and immune suppression in cancer patients) that have hindered the generation of effective antitumor immune responses. Improvements in genomics technology in the area of DNA microarrays and differential display and subtractive hybridization together with a new wave of mass spectrometry-based proteomics tools, as well as more sensitive assays to validate the immunoreactivity of new antigens, have all accelerated the rate of new antigen discovery in cancer. This rapid progress should initiate a major paradigm shift in how we treat cancer within the next 10 years, where, instead of being a novelty, the combination of targeted T cell-based vaccines and antiangiogenesis therapies will be routinely combined with traditional chemotherapy. The successful combination of these approaches will change the face of cancer from a relatively acute, life-threatening disease to a manageable chronic disorder with long survival times.