title: Immunization of high-risk breast cancer patients with clustered sTn-KLH conjugate plus the immunologic adjuvant QS-21.
abstract: OBJECTIVE
  To determine the clinical toxicities and antibody response against sTn and tumor cells expressing sTn following immunization of high-risk breast cancer patients with clustered sTn-KLH [sTn(c)-KLH] conjugate plus QS-21.
  
  
  METHODS
  Twenty-seven patients with no evidence of disease and with a history of either stage IV no evidence of disease, rising tumor markers, stage II (>or=4 positive axillary nodes), or stage III disease received a total of five injections each during weeks 1, 2, 3, 7, and 19. Immunizations consisted of sTn(c)-KLH conjugate containing 30, 10, 3, or 1 microg sTn(c) plus 100 microg QS-21. Induction of IgM and IgG antibodies against synthetic sTn(c) and natural sTn on ovine submaxillary mucin were measured before and after therapy. Fluorescence-activated cell sorting analyses assessed reactivity of antibodies to LSC and MCF-7 tumor cells.
  
  
  RESULTS
  The most common toxicities were transient local skin reactions at the injection site and mild flu-like symptoms. All patients developed significant IgM and IgG antibody titers against sTn(c). Antibody titers against ovine submaxillary mucin were usually of lower titers. IgM reactivity with LSC tumor cells was observed in 21 patients and with MCF-7 cells in 13 patients. There was minimal IgG reactivity with LSC cells.
  
  
  CONCLUSIONS
  Immunization with sTn(c)-KLH conjugate plus QS-21 is well tolerated and immunogenic in high-risk breast cancer patients. Future trials will incorporate sTn(c) as a component of a multiple antigen vaccine.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. gilewskt@mskcc.org
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Gilewski
authors.forename: Govind
authors.initials: G
authors.lastname: Ragupathi
authors.forename: Maura
authors.initials: M
authors.lastname: Dickler
authors.forename: Shemeeakah
authors.initials: S
authors.lastname: Powell
authors.forename: Sonal
authors.initials: S
authors.lastname: Bhuta
authors.forename: Kathy
authors.initials: K
authors.lastname: Panageas
authors.forename: R Rao
authors.initials: RR
authors.lastname: Koganty
authors.forename: Jeannette
authors.initials: J
authors.lastname: Chin-Eng
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Alan N
authors.initials: AN
authors.lastname: Houghton
authors.forename: Philip O
authors.initials: PO
authors.lastname: Livingston
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000906:Antibodies / Q000097:blood; D001943:Breast Neoplasms / Q000473:pathology / Q000517:prevention & control*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007114:Immunization; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D012306:Risk; D012503:Saponins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D019496:Cancer Vaccines; D007075:Immunoglobulin M; D012503:Saponins; C099077:sialyl-Tn antigen-keyhole-limpet hemocyanin conjugate; C078785:saponin QA-21V1