The use of carbohydrate antigens for the preparation of vaccines for therapy in breast cancer.

Abstract

Immunotherapy of human breast cancer is a rapidly growing experimental area based on peptidic as well as carbohydrate tumor-associated antigens. Cell surface carbohydrates are characteristic of different stages of normal development and differentiation; distinct carbohydrates are expressed in tissue- and cell-specific manners during those processes. Under pathological conditions such as neoplasia, changes in carbohydrate structures can almost always be present. In the successful development of carbohydrate anticancer vaccines, adjuvant and carrier molecules that promote the presentation of an antigen to the immune effector cells are prominent factors. At present, keyhole limpet hemocyanin (KLH) is the most widely used carrier protein in cancer immunotherapy, and QS-21 is the adjuvant most widely employed. In breast cancer, the immunogenicity of TF, Tn, STn and globo H antigens has been explored in different clinical trials. Approaches including vaccines against STn and globo H are presently being assayed with expectancy. From the experience obtained, it is possible to conclude that: 1) the employment of glycolipopeptide with clustered epitopes seems to be more effective than that of related structures with single epitopes in inducing antitumor cell antibodies; 2) the conjugation to carriers is best achieved using KLH; 3) totally synthetic constructs can be better immunogens in conjunction with a suitable adjuvant such as QS-21; in some cases, this adjuvant leads to a bypass in the need for specific T-cell help to stimulate IgG as well as IgM antibodies. In other cases, a T-cell mediated immune response is obtained, and (4) the development of a totally synthetic vaccine would greatly facilitate the production of the vaccine for large scale clinical trials with the attainment of regulatory approval.