A large-scale immunohistology screen was initiated by the group of physician-scientist Philip O. Livingston to identify the dominant cell-surface antigens expressed by common human cancers. A series of studies was conducted in mice and in patients to identify the most-potent vaccines for inducing antibodies against these antigens.
In every case, the best antibody response was induced by covalently linking the antigen to the large carrier molecule keyhole limpet hemocyanin (KLH), which is obtained from the keyhole limpet, a mollusk. The optimal adjuvants were purified saponin fractions or semisynthetic saponins, all derived from the bark of a South American tree.
These vaccines have induced consistent antibodies against a series of cell-surface carbohydrate and protein antigens including GM2, GD2, GD3, fucosyl GM1, and sialyl Lewis a (also known as CA19.9) gangliosides; the neutral glycolipid globo H; blood-group-related antigens Tn, sialyl Tn, and Thompson Friedenreich antigen (TF); and mucin 1 (MUC1).
More recently, in work performed by Memorial Sloan Kettering’s Clinical Grade Production Facility, these individual monovalent vaccines have been combined into polyvalent vaccines containing three to seven different conjugates. A series of phase II clinical trials in patients with ovarian cancer, sarcoma, and neuroblastoma was designed to determine whether vaccine-induced antibodies against multiple cell-surface antigens are able to prolong disease-free survival and overall survival after surgical resection or chemotherapeutic response of all known disease.
These studies include ongoing, multicenter, randomized trials in ovarian cancer patients who are in second complete remission, and stage IV sarcoma patients who have been treated with surgery. Human monoclonal antibodies are prepared from the B cells of these immunized patients in collaboration with MabVax Therapeutics, Inc.