Le and Globo H Vaccines

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The development of Ley and Globo H vaccines was previously limited by the lack of sufficient quantities of antigen for vaccine construction and testing. Over the last 6 yr, Dr. Samuel Danishefsky in our group has successfully synthesized both antigens (76-78). We have immunized groups of mice with Globo H-ceramide plus or minus adjuvants QS-21 and Salmonella Minnesota mutant R595, and with Globo H covalently attached to KLH or bovine serum albumin (BSA) plus immunological adjuvants QS-21 or GPI-0100. The highest antibody titers against both synthetic antigen and MCF7 cells expressing Globo H were induced by the Globo H-KLH plus QS-21 vaccine (77). The antibody titer induced against synthetic Globo H was 1/120,000 by ELISA, the titer induced against MCF7 was 1/320, and potent complement-mediated cytotoxicity was seen as well. Ley-BSA and Ley-KLH vaccines have also been tested in the mouse. High-titer antibody responses have resulted against the synthetic epitope of Ley and against tumor cells expressing Ley in the majority of mice immunized (80). Based on these results, clinical trials with Globo H-KLH plus QS-21 and Ley-KLH plus QS21 have been initiated in patients with breast, prostate, or ovary cancer. The results are summarized in Table 3. Antibodies against the purified antigens and against tumor cells expressing these antigens were induced in most patients immunized with globo H (79; see Fig. 3) and occasional patients immunized with Ley (81-83).

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