Peptide mimotopes as prototypic templates of broad-spectrum surrogates of carbohydrate antigens for cancer vaccination

Abstract

Mechanisms of broad cross-protection, as seen in viral infection and also applied to vaccines, emphasize preexisting antibodies, CD8+ memory T cells, and accelerated B-cell responses reactive with conserved regions in antigens. Another practical application to induce broad-spectrum responses is making use of multispecific antigen recognition by antibodies and T cells. Antibody polyreactivity can be related to the capacity of the antigen-combining site to accommodate a number of different small epitopes or to attain different conformations. A better understanding of the functionality of molecular interactions with graded specificity might help the design of polyreactive immunogens inducing antibody responses to a predefined set of target antigens. We have found this approach useful in targeting tumor-associated carbohydrate antigens in cancer vaccine development. Using combinatorial libraries and pharmacophore design principles, carbohydrate mimetic peptides were created that not only induce antibodies with multiple specificities, but also cellular responses that inhibit tumor growth in vivo.