Carbohydrate vaccines that induce antibodies against cancer. 2. Previous experience and future plans

Abstract

The primary function of antibodies is the elimination of circulating viral or bacterial pathogens from the blood-stream, lymphatics and interstitial spaces, and so, once induced, antibodies should be ideally suited for eliminating tumor cells and micrometastases from these spaces as well. Natural or tumor-induced and vaccine-induced antibodies against human cancer-associated antigens have been correlated with an improved clinical outcome. In the mouse, passive administration of monoclonal antibodies against cell-surface antigens 1–4 days after tumor challenge, and active induction of antibodies with vaccines, has resulted in prolonged survival or complete protection from tumor growth. This is a setting similar to the adjuvant setting in humans. Carbohydrates are the most abundant antigens at the cell surface of cancer cells, where they play important roles in cell-cell interactions, proliferation and the metastatic process. They have been shown to be excellent targets for immune attack by antibodies against human cancers, especially in the adjuvant setting. Vaccines containing these carbohydrate antigens covalently attached to immunogenic carrier proteins, such as KLH, plus potent immunological adjuvants, such as QS-21, effectively induce antibodies against these antigens in patients, which can result in complement-mediated lysis of antigen-positive tumor cells. Phase III trials with KLH conjugate vaccines have been initiated in the adjuvant setting against two carbohydrate antigens, the ganglioside GM2 and the blood-group-related antigen sTn. As the immunogenicity of additional vaccines is confirmed in small pilot trials, trials with polyvalent vaccines against two to five different antigens tailored for particular cancer types are planned.