title: Different adjuvanticity of incomplete freund's adjuvant derived from beef or vegetable components in melanoma patients immunized with a peptide vaccine.
abstract: Adjuvants are requisite components of many vaccines designed to elicit T-cell immunity although the exact components of commonly used adjuvants are not always fully defined. In 2006, owing to concerns of prion contamination, the formulation of Montanide ISA 51 Incomplete Freund's Adjuvant (IFA) was changed from using oleic acid isolated from beef tallow to that isolated from olives. In sequential clinical trials in the Surgery Branch, NCI patients at high risk for recurrence of melanoma were immunized with the gp100 melanoma/melanocyte antigenic peptide, gp100: 209-217 (210M), emulsified in the beef-derived IFA or the olive-derived IFA. The in vivo generation of gp100 reactive T cells was significantly less in patients receiving the olive compared with the beef IFA as assessed by both ELISPOT (P2=0.0001) and in vitro sensitization assays (P2=0.0001). Local skin reactions to the peptide emulsion were also far less severe using the olive IFA (P2=0.0003). Thus it seems likely that contaminants in the beef-derived IFA played an important role in the increased adjuvanticity of this preparation compared with the olive-derived IFA. These findings raise serious concerns related to the use of the available olive-derived IFA for immunization in clinical trials. A survey of ongoing clinical trials listed in ClinicalTrials.gov revealed 36 trials currently accruing patients that are using the olive-derived Montanide ISA 51 IFA.
authors.affiliation: Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1201, USA. SAR@nih.gov
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Udai S
authors.initials: US
authors.lastname: Kammula
authors.forename: Marybeth S
authors.initials: MS
authors.lastname: Hughes
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.forename: Susan L
authors.initials: SL
authors.lastname: Schwarz
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Morton
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Laurencot
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sherry
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism; D000818:Animals; D019496:Cancer Vaccines; D002417:Cattle; D002461:Cell Line, Transformed; D005223:Fats / Q000378:metabolism; D005620:Freund's Adjuvant / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D006801:Humans; D007114:Immunization; D008353:Mannitol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D031658:Olea / Q000378:metabolism; D009829:Oleic Acids / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome; D022223:Vaccines, Subunit; D014675:Vegetables / Q000378:metabolism; D058951:gp100 Melanoma Antigen / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D005223:Fats; D009829:Oleic Acids; C548637:PMEL protein, human; D022223:Vaccines, Subunit; D058951:gp100 Melanoma Antigen; C477385:montanide ISA 51; D008353:Mannitol; D005620:Freund's Adjuvant; C013698:tallow