Augmenting the immunogenicity of carbohydrate tumor antigens.

Antibody responses have identified cell surface carbohydrate antigens as potentially immunogenic cancer antigens in a variety of different tumors, but immunization with whole tumor cells or cell lysates has only occasionally induced immune responses against these antigens. Three approaches to further augmenting their immunogenicity have been explored, mixture with immunological adjuvants, synthesis of more immunogenic derivatives and conjugation to immunogenic proteins. Conjugation to proteins such as KLH plus the use of potent adjuvants such as QS-21 proved most immunogenic. Carbohydrate epitopes on gangliosides (GM2 and GD2), neutral glycolipids (Ley and Globo H) and glycoproteins (Ley, Globo H, TF, sTn and Tn) are of special interest. Each of these antigens has been synthesized and conjugated to KLH. Their use in preclinical or clinical vaccination studies has resulted in increased IgM and IgG antibody responses against tumors expressing these antigens. Phase I-II clinical trials in patients with cancer have been initiated with each to optimize immunogenicity. The GM2 vaccine has progressed to Phase III trials and the sTn vaccine to Phase II trials aimed at determining the impact of vaccination on survival.