Immunization of ovarian cancer patients with a synthetic Lewisy-protein conjugate vaccine: A phase 1 trial

✍ Scribed by Paul J. Sabbatini; Valery Kudryashov; Govindaswami Ragupathi; Samuel J. Danishefsky; Philip O. Livingston; William Bornmann; Maria Spassova; Andrzej Zatorski; David Spriggs; Carol Aghajanian; Steven Soignet; Madeline Peyton; Catherine O'Flaherty; John Curtin; Kenneth O. Lloyd

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: French
• Weight: 138 KB
• Volume: 87
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/1097-0215(20000701)87:1<79::aid-ijc12>3.0.co;2-l

✦ Synopsis

As the initial step in developing carbohydrate-based vaccines for the treatment of ovarian cancer patients in an adjuvant setting, 25 patients were immunized 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 g of carbohydrate 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 -ceramide and Le y mucin) and by flow cytometry and a complement-dependent cytoxicity assay for reactivity with Le y -expressing tumor cells. The majority of the patients (16/24) produced anti-Le y antibodies as assessed by ELISA, and a proportion of these had strong anti-tumor cell reactivity as assessed by flow cytometry and complement-dependent cytotoxicity. One serum, analyzed in detail, was shown to react with glycolipids but not with glycoproteins or mucins expressed by ovarian cancer cell line OVCAR-3. The vaccine was well tolerated and no gastrointestinal, hematologic, renal, or hepatic toxicity 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 consideration for the therapy of epithelial cancers. Int.