Immunization of ovarian cancer patients with a synthetic Lewis(y)-protein conjugate vaccine: a phase 1 trial.
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 microg 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.
Sabbatini
P J
PJ
Department of Medicine, Division of Developmental Chemotherapy, Memorial Hospital, New York, New York, USA.
Kudryashov
V
V
Ragupathi
G
G
Danishefsky
S J
SJ
Livingston
P O
PO
Bornmann
W
W
Spassova
M
M
Zatorski
A
A
Spriggs
D
D
Aghajanian
C
C
Soignet
S
S
Peyton
M
M
O'Flaherty
C
C
Curtin
J
J
Lloyd
K O
KO
D000276:Adjuvants, Immunologic; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines; D002240:Carbohydrate Sequence; D018269:Carcinoma, Endometrioid / Q000276:immunology / Q000628:therapy; D002855:Chromatography, Thin Layer; D018283:Cystadenocarcinoma, Papillary / Q000276:immunology / Q000628:therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006433:Hemocyanins / Q000627:therapeutic use; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000627:therapeutic use*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000628:therapy*; D012503:Saponins / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D018074:Vaccines, Conjugate
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D012503:Saponins; D018074:Vaccines, Conjugate; C078785:saponin QA-21V1; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin