Immunization of ovarian cancer patients with a synthetic Lewis(Y)-protein conjugate vaccine: A phase 1 trial

Citation
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
Citations number
22
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF CANCER
ISSN journal
00207136 → ACNP
Volume
87
Issue
1
Year of publication
2000
Pages
79 - 85
Database
ISI
SICI code
0020-7136(20000701)87:1<79:IOOCPW>2.0.ZU;2-C
Abstract
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.