Keyhole limpet hemocyanin conjugate vaccines against cancer: The Memorial Sloan Kettering experience

摘要

Passively administered and actively induced antibodies have been associated with the eradication of circulating tumor cells and micrometastases in mice and humans. We have identified a series of cell surface carbohydrate and peptide antigens on melanomas, sarcomas, and cancer of the breast, prostate, ovary, and lung tissues. We found that breaking tolerance toward these tumor antigens was best achieved using vaccines containing antigens chemically conjugated to keyhole limpet hemocyanin (KLH) plus a potent immunological adjuvant (QS-21). To date, by using this approach to vaccination, antibodies have been induced in patients against glycolipid . antigens GM2, GD2, GD3, Fucosy1GM1, Globo H, and Lewis Y, and glycoprotein (mucin) antigens Tn, sialyl Tn, TF, and MUCL More recently, in a comparative study we investigated the T cell response induced by MUC1-KLH conjugates. Although a MUC1-specific T cell response was not consistently detected in any patient, the role of KLH in orienting the cytokine environment was crucial. We were able to confirm that KLH in these conjugate vaccines induces a Th1 T cell response as demonstrated by the high anti-KLH INF-7 secretion and the IgG1 and IgG3 subclasses of this high titer IgG antibodies induced. Clinical trials using KLH conjugated glycolipid and glycoprotein vaccines, are currently ongoing. These range from phase I/II single antigens trials with glycosilated MUC1, polysialic acid, synthetic Fucosyl GM1 and GD2, to phase II trials with a polyvalent vaccine containing six or seven antigens. Randomized phase 11 trials with polyvalent vaccines are planned for initiation in 2001–2002 in patients with ovarian, breast, and prostate cancer.