Novel vaccines for the treatment of gastrointestinal cancers

Continuing advances in immunology and molecular biology during the past several decades have provided optimism that immunomodulatory strategies may be clinically useful in patients with cancer. Key advances have included: (1) recognition of the critical role of the antigen-presenting cell and greatly improved understanding of antigen processing and presentation, including the molecular interactions between HLA molecules and antigenic epitopes on the antigen-processing cell and the receptors on T cells, and (2) the roles of costimulatory molecules such as B7.1, ICAM-1, and LFA-3 in the induction and maintenance of an immune response. In addition, new techniques have allowed us to identify immunogenic antigenic determinants, alter their binding affinities, and evaluate the overall success of the intervention through both in vivo and in vitro assays. Carcinoembryonic antigen (CEA) is overexpressed in a large number of gastrointestinal, lung, and breast cancers. Clinical trials have established treatment protocols using viral vectors to immunize patients to CEA without producing deleterious autoimmune phenomena. By combining various vectors to include MUC-1 and/or CEA plus costimulatory molecules in a prime-and-boost regimen, we are beginning to see signs that this intervention can not only produce changes in immune function but also potentially improve clinical outcomes. Phase III studies to test these hypotheses are under way.