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.