VACCINES IN THE TREATMENT OF CANCER

The development of vaccines for treating cancer is discussed. The cent ral hypothesis behind active specific immunotherapy for cancer is that tumor cells express unique antigens that tell the immune system that something about these cells is foreign. A vaccine is a way of deliveri ng an antigen to the immune system such that immune cells recognize th e antigen as foreign and destroy any cells bearing that antigen. Early trials of vaccines for treating cancer were limited by technical prob lems related to poor knowledge of the immune system. Recent research h as focused on expression on the surfaces of antigen-presenting cells o f antigenic peptides bound to major histocompatibility complex (MHC) m olecules, peptide recognition by cytotoxic T cells, and the requiremen t for a second signal, such as the costimulatory molecule B7, for T-ce ll activation. Antigenic peptides constitute the ''keys'' that open th e ''locks'' of T cells; the problem is that researchers have difficult y choosing the right keys from among the myriad available. Administeri ng an adjuvant enhances the immune response by making the antigen more recognizable as foreign. Vaccine preparation techniques include pepti de pulsing (a method for boosting cell-surface expression of the antig enic peptide-MHC combinations), intramuscular injections of DNA plasmi ds encoding the desired antigen, and gene insertion into vaccinia viru s by recombinant DNA technology. Cancer vaccines may be administered b y scarification, by subcutaneous and intramuscular injection, and intr anasally. Clinical trials of cancer vaccines continue to encounter pro blems because of the many variables in administration routes, dosages, patient populations, and methods for evaluating responses. There have been some promising results but also many treatment failures. Antigen targets in trials today include normal antigens that have a limited n ormal-tissue distribution or expression (e.g., carcinoembryonic antige n), viral proteins (e.g., E6 protein of human papillomavirus), and mut ated oncogenes. Toxicities have been mild. Better understanding of the immune system and better technology have led to advances in the devel opment of vaccines for treating cancer, but there is still much progre ss to achieve.