Development of optimized cryptic peptides for immunotherapy

Specific immunotherapy is based on the use of tumor-specific antigens to induce an efficient antitumor immune response. Although tumors are known to be weakly immunogenic and therefore capable of escaping immune surveillance, the objective of tumor vaccination is to induce a frequent, strong and long-lasting antitumor immune response based mainly on the activation of cytotoxic T-lymphocytes. However, as widely expressed tumor antigens (universal tumor antigens) often correspond to normal proteins expressed not only by tumor cells but also by normal cells and tissues, these antigens are generally tolerated by the immune system. Thus, circumventing self tolerance to universal tumor antigens is a major goal of cancer vaccine research. Disappointing results obtained to date with most tumor vaccines has led to a shift in research toward determining ways of stimulating the immune response through the use of new adjuvants, immunostimulants and delivery vectors. However, although these aspects are clearly crucial to vaccine development, breakthroughs in the field may lie in the use of strong antigens as optimized cryptic peptides derived from universal tumor antigens, combined with a potent adjuvant. Targeting cryptic tumor peptides/antigens is an efficient way of overcoming tolerance. Indeed, the first vaccine based on an optimized cryptic peptide induced strong antitumor immunity and demonstrated promising clinical activity.