SEROLOGICAL RESPONSE PATTERNS OF MELANOMA PATIENTS IMMUNIZED WITH A GM2 GANGLIOSIDE CONJUGATE VACCINE

Gangliosides, such as GM2, GD2, GD3, and 9-O-acetyl GD3, are receiving attention as targets for antibody-based and vaccine-based therapies o f melanoma, GM2 appears to be a particularly immunogenic ganglioside i n humans, as indicated by the presence of naturally occurring IgM anti -GM2 antibodies in approximate to 5% of humans and the fact that immun ization with irradiated GM2-expressing melanoma cells or purified GM2 adherent to bacillus Calmette-Guerin elicits GM2 antibodies of low to moderate titers in a high proportion of vaccinated patients, To develo p vaccines that consistently induce high titers of IgM as well as IgG anti-GM2 antibodies, vaccines containing GM2 conjugated to keyhole lim pet hemocyanin as the carrier protein and QS-21 as the adjuvant have b een constructed. The serological response of vaccinated patients was m onitored by ELISA using purified GM2 ganglioside for IgM and IgG anti- GM2 antibodies and for GM2 cell surface-reactive antibodies by immune adherence assays and cytotoxic tests (IgM antibodies) and mixed hemads orption assays (IgG antibodies). The majority of vaccinated patients d eveloped IgM and IgG antibodies detectable by ELISA. In most cases, th e results of IgM ELISA correlated with assays for cell surface-reactiv e IgM antibodies. This was not true for IgG anti-GM2 antibodies, where strong discrepancies were seen between high titers in ELISA and littl e or no reactivity in mixed hemadsorption tests for cell surface-react ive antibodies. These IgG antibodies (and the less frequent IgM antibo dies that show similar discrepancies) may be directed against GM2 dete rminants that are buried, hidden, or not present on GM2-expressing tar get cells, With regard to a major objective of ganglioside vaccines-i. e., generation of cytotoxic antibodies-the GM2-keyhole limpet hemocyan in/QS-21 vaccine is clearly superior to the previously tested GM2/baci llus Calmette-Guerin vaccine. However, variability in patient response and lack of persistence of high-titered IgM cytotoxic antibodies in m any patients are problems that remain to be solved.