title: Pilot study of a heptavalent vaccine-keyhole limpet hemocyanin conjugate plus QS21 in patients with epithelial ovarian, fallopian tube, or peritoneal cancer.
abstract: OBJECTIVE
  To characterize the safety and immunogenicity of a heptavalent antigen-keyhole limpet hemocyanin (KLH) plus QS21 vaccine construct in patients with epithelial ovarian, fallopian tube, or peritoneal cancer in second or greater complete clinical remission.
  
  
  METHODS
  Eleven patients in this pilot trial received a heptavalent vaccine s.c. containing GM2 (10 microg), Globo-H (10 microg), Lewis Y (10 microg), Tn(c) (3 microg), STn(c) (3 microg), TF(c) (3 microg), and Tn-MUC1 (3 microg) individually conjugated to KLH and mixed with adjuvant QS21(100 microg). Vaccinations were administered at weeks 1, 2, 3, 7, and 15. Periodic blood and urine samples were obtained to monitor safety (complete blood count, comprehensive panel, amylase, thyroid-stimulating hormone, and urinalysis) and antibody production (ELISA, fluorescence-activated cell sorting, and complement-dependent cytotoxicity).
  
  
  RESULTS
  Eleven patients were included in the safety analysis; 9 of 11 patients remained on study for at least 2 weeks past fourth vaccination and were included in the immunologic analysis (two withdrew, disease progression). The vaccine was well tolerated. Self-limited and mild fatigue (maximum grade 2 in two patients), fever, myalgia, and localized injection site reactions were most frequent. No clinically relevant hematologic abnormalities were noted. No clinical or laboratory evidence of autoimmunity was seen. Serologic responses by ELISA were largely IgM against each antigen with the exception of Tn-MUC1 where both IgM and IgG responses were induced. Antibody responses were generally undetectable before immunization. After immunization, median IgM titers were as follows: Tn-MUC1, 1:640 (IgG 1:80); Tn, 1:160; TF, 1:640; Globo-H, 1:40; and STn, 1:80. Only one response was seen against Lewis Y; two were against GM2. Eight of nine patients developed responses against at least three antigens. Antibody titers peaked at weeks 4 to 8 in all patients. Fluorescence-activated cell sorting and complement-dependent cytotoxicity analysis showed substantially increased reactivity against MCF7 cells in seven of nine patients, with some increase seen in all patients.
  
  
  CONCLUSIONS
  This heptavalent-KLH conjugate plus QS21 vaccine safely induced antibody responses against five of seven antigens. Investigation in an adequately powered efficacy trial is warranted.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. sabbatip@mskcc.org
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Sabbatini
authors.forename: Govind
authors.initials: G
authors.lastname: Ragupathi
authors.forename: Chandra
authors.initials: C
authors.lastname: Hood
authors.forename: Carol A
authors.initials: CA
authors.lastname: Aghajanian
authors.forename: Margrit
authors.initials: M
authors.lastname: Juretzka
authors.forename: Alexia
authors.initials: A
authors.lastname: Iasonos
authors.forename: Martee L
authors.initials: ML
authors.lastname: Hensley
authors.forename: Maria K
authors.initials: MK
authors.lastname: Spassova
authors.forename: Ouathek
authors.initials: O
authors.lastname: Ouerfelli
authors.forename: David R
authors.initials: DR
authors.lastname: Spriggs
authors.forename: William P
authors.initials: WP
authors.lastname: Tew
authors.forename: Jason
authors.initials: J
authors.lastname: Konner
authors.forename: Henrik
authors.initials: H
authors.lastname: Clausen
authors.forename: Nadeem
authors.initials: N
authors.lastname: Abu Rustum
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Dansihefsky
authors.forename: Philip O
authors.initials: PO
authors.lastname: Livingston
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use / Q000633:toxicity; D000328:Adult; D004359:Drug Therapy, Combination; D005185:Fallopian Tube Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D006433:Hemocyanins / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D008875:Middle Aged; D008958:Models, Molecular; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000276:immunology* / Q000473:pathology; D012449:Safety; D012503:Saponins / Q000627:therapeutic use* / Q000633:toxicity; D018074:Vaccines, Conjugate / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D000276:Adjuvants, Immunologic; D012503:Saponins; D018074:Vaccines, Conjugate; C078785:saponin QA-21V1; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin