Sf. Slovin et al., Carbohydrate vaccines in cancer: Immunogenicity of a fully synthetic globoH hexasaccharide conjugate in man, P NAS US, 96(10), 1999, pp. 5710-5715
Citations number
24
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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.