Pj. Sabbatini et al., Immunization of ovarian cancer patients with a synthetic Lewis(Y)-protein conjugate vaccine: A phase 1 trial, INT J CANC, 87(1), 2000, pp. 79-85
As the initial step in developing carbohydrate-based vaccines for the treat
ment of ovarian cancer patients in an adjuvant setting, 25 patients were im
munized with a Lewis(y) pentasaccharide (Le(y))-keyhole limpet hemocyanin (
KLH)-conjugate vaccine together with the immunological adjuvant QS-21. Four
different doses of the vaccine, containing 3, 10, 30, and 60 mu g of carbo
hydrate were administered s.c, at 0, 1, 2, 3, 7, and 19 weeks to groups of
6 patients. Sera taken from the patients at regular intervals were assayed
by ELISA for reactivity with naturally occurring forms of Le(y) (Le(y)-cera
mide and Le(y) mucin) and by flow cytometry and a complement-dependent cyto
xicity assay for reactivity with Le(y)-expressing tumor cells. The majority
of the patients (16/24) produced anti-Le(y) antibodies as assessed by ELIS
A, and a proportion of these had strong anti-tumor cell reactivity as asses
sed by flow cytometry and complement-dependent cytotoxicity. One serum, ana
lyzed in detail, was shown to react with glycolipids but not with glycoprot
eins or mucins expressed by ovarian cancer cell line OVCAR-3. The vaccine w
as well tolerated and no gastrointestinal, hematologic, renal, or hepatic t
oxicity related to the vaccine was observed, On the basis of this study, Le
(y)-KLH should be a suitable component for a polyvalent vaccine under consi
deration for the therapy of epithelial cancers. Int. J. Cancer 87:79-85, 20
00. (C) 2000 Wiley-Liss, Inc.