PEPTIDE MIMICRY OF ADENOCARCINOMA-ASSOCIATED CARBOHYDRATE ANTIGENS

Carbohydrate antigens have been identified as significant antigens in many human tumors either by analyzing antibodies in patients' sera or by using monoclonal antibodies of either mouse or human origin, Three carbohydrate epitopes present on cancer-associated mucins [sialyl-Lewi s A (SLA), sialyl-Lewis X (SLX), and siayl-Tn (STn)] may have function al significance in metastasis, Subsequently, these antigens are consid ered as targets for active specific immunotherapy. Carbohydrates, as T -cell-independent antigens, often elicit diminished immune responses, To overcome this drawback, carbohydrates are typically coupled to prot ein carriers to elicit immunoglobulin G (IgG) responses as opposed to low-affinity IgM responses, which oftentimes accompanies carbohydrate- based immunizations, In addition, some complex carbohydrates are diffi cult to synthesize, This latter aspect is further magnified if one con siders that clustering of epitopes on neoglycoproteins must be emulate d in the synthesis process, leading to multiple presentation or tandem repeats of the synthetic carbohydrate immunogen, Here, we examine the hypothesis that peptides that mimic carbohydrates might be developed to induce immune responses that target and mediate the killing of tumo r cells, particularly breast cancer cells in an adjuvant-type setting, We have found that carbohydrate-mimicking peptides retain carbohydrat e-like conformations, inducing anti-carbobydrate immune responses agai nst breast tumor cells and mediating their killing by a complement-dep endent mechanism.