Peptide mimicry of adenocarcinoma-associated carbohydrate antigens.

Abstract

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-Lewis A (SLA), sialyl-Lewis X (SLX), and sialyl-Tn (STn)] may have functional significance in metastasis. Subsequently, these antigens are considered 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 protein carriers to elicit immunoglobulin G (IgG) responses as opposed to low-affinity IgM responses, which often times accompanies carbohydrate-based immunizations. In addition, some complex carbohydrates are difficult to synthesize. This latter aspect is further magnified if one considers that clustering of epitopes on neoglycoproteins must be emulated 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 tumor cells, particularly breast cancer cells in an adjuvant-type setting. We have found that carbohydrate-mimicking peptides retain carbohydrate-like conformations, inducing anti-carbohydrate immune responses against breast tumor cells and mediating their killing by a complement-dependent mechanism.