We have previously reported on a
carbohydrate-based
vaccine program for
immunotherapy in
cancer patients. One such
vaccine, based on the
globo H antigen conjugated to the
protein keyhole limpet hemocyanin (KLH), has been in clinical evaluation. Although this and other
carbohydrate vaccines have been shown to induce antibody responses, there are currently no quantitative data on the antibody levels achieved in immunized patients by these or other anti-
cancer vaccines. We report herein an efficient route to complex synthetic
oligosaccharides attached to an affinity matrix for identifying and isolating
antibodies elicited against such a
carbohydrate-based
vaccine in humans. Pre- and postvaccination profiles from serum samples of patients immunized with
globo H-KLH were compared. All anti-
globo H antibody activity was efficiently separated from other serum constituents. The isolated
antibodies were readily quantified, and their specificities were analyzed. Since no comparable data were available on
antibodies resulting from the vaccination of other
cancer patients, we compared the observed levels with those quoted in studies with bacterial
polysaccharide vaccines that had been quantified. Remarkably,
cancer patients immunized with
globo H-KLH produce anti-
globo H antibody levels often exceeding those formed by immunization with
bacterial polysaccharides. In addition, substantial quantities of both
IgG and
IgM antibodies were elicited, clearly indicating a class switch to
IgG. Taken together, these analyses serve to clarify several aspects of the immune response to the
vaccine and give several new insights to the
carbohydrate-based vaccination strategy. Furthermore,
antibodies so isolated could well have applications in clinical
therapy.