Carbohydrate vaccines in cancer: Immunogenicity of a fully synthetic globoH hexasaccharide conjugate in man

The complex carbohydrate molecule globe H hexasaccharide has been synthesiz ed, conjugated to keyhole limpet hemocyanin, and administered with the immu nologic adjuvant QS-21 as a vaccine for patients with prostate cancer who h ave relapsed after primary therapies such as radiation or surgery, Globe H is one of several candidate antigens present on prostate cancer cells that can serve as targets for immune recognition and treatment strategies. The v accine, given as five subcutaneous vaccinations over 26 weeks, has been sho wn to be safe and capable of inducing specific high-titer IgM antibodies ag ainst globe H. Its immunogenicity was confirmed in prostate cancer patients with a broad range of stages and tumor burdens. Observations of several pa tients who had evidence of disease relapse restricted to a rising biochemic al marker, prostate-specific antigen (PSA), indicated that a treatment effe ct could occur within 3 months after completion of the vaccine therapy. Thi s effect was manifested as a decline of the slope of the log of PSA concent ration vs, time plot after treatment compared with values before treatment. Five patients continue to have stable PSA slope profiles in the absence of any radiographic evidence of disease for more than 2 years, The concept of using PSA slope profiles in assessing early treatment effects in biologica l therapies such as vaccines awaits further validation in phase II and III trials. The use of a variety of lesser known candidate glycoprotein and car bohydrate antigens in prostate cancer serves as a focus for the development of a multivalent vaccine of the treatment of relapsed prostate cancer in p atients with minimal tumor burden.