title: A bivalent conjugate vaccine in the treatment of biochemically relapsed prostate cancer: a study of glycosylated MUC-2-KLH and Globo H-KLH conjugate vaccines given with the new semi-synthetic saponin immunological adjuvant GPI-0100 OR QS-21.
abstract: GPI-0100 is a semi-synthetic saponin with modifications designed to augment stability and diminish toxicity. Two batches of GPI-0100 (the second with higher purity) were tested with doses ranging between 100 and 5000 microg in groups of five treated prostate cancer patients who had no evidence of disease except for rising PSA levels. GPI-0100 was mixed with a bivalent vaccine containing the glycolipid Globo H and the glycosylated mucin MUC2 conjugated to keyhole limpet hemocyanin (KLH). All doses were well tolerated and antibody titers against Globo H and MUC-2 escalated with the increasing dose levels. At the 5000 microg dose level in this patient population, toxicity remained minimal with only occasional grade II local toxicity at vaccination sites and occasional sporadic grade I elevations in ALT. Compared with a subsequent trial with the same bivalent vaccine plus QS-21 at the maximal tolerated dose of 100 microg, the 5000 microg dose of GPI-0100 produced comparable antibody titers.
authors.affiliation: Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. slovins@mskcc.org
authors.forename: Susan F
authors.initials: SF
authors.lastname: Slovin
authors.forename: Govind
authors.initials: G
authors.lastname: Ragupathi
authors.forename: Celina
authors.initials: C
authors.lastname: Fernandez
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Jefferson
authors.forename: Meghan
authors.initials: M
authors.lastname: Diani
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Wilton
authors.forename: Shemeeakah
authors.initials: S
authors.lastname: Powell
authors.forename: Maria
authors.initials: M
authors.lastname: Spassova
authors.forename: Celso
authors.initials: C
authors.lastname: Reis
authors.forename: Henrick
authors.initials: H
authors.lastname: Clausen
authors.forename: Samuel
authors.initials: S
authors.lastname: Danishefsky
authors.forename: Philip
authors.initials: P
authors.lastname: Livingston
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007115:Immunization Schedule; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000628:therapy*; D012008:Recurrence; D012503:Saponins / Q000009:adverse effects / Q000627:therapeutic use*; D018074:Vaccines, Conjugate / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; C484998:GPI0100; C502357:MUC-2-KLH vaccine; D012503:Saponins; D018074:Vaccines, Conjugate; C502358:globo H-KLH vaccine; C078785:saponin QA-21V1; D017430:Prostate-Specific Antigen