title: Immunogenicity for CD8+ and CD4+ T cells of 2 formulations of an incomplete freund's adjuvant for multipeptide melanoma vaccines.
abstract: An incomplete Freund's adjuvant (IFA) commonly used in experimental cancer vaccines has recently been reformulated. Oleic acid used in the surfactant was purified from a vegetable source (olives, IFA-VG) rather than an animal source (beef tallow, IFA-AN). To provide an insight into the adjuvant properties of the new formulation, we reviewed T-cell responses, by enzyme-linked immunospot assay, to multipeptide vaccines in 2 sequential clinical trials that spanned this transition of adjuvants. Analyses included 194 patients who received either IFA-AN or IFA-VG for all vaccines, and a subset of 93 patients best matched by study arm for vaccine antigens (12 melanoma peptides restricted by major histocompatibility complex class I, 12MP; plus a tetanus helper peptide, tet) administered with IFA but without granulocyte macrophage-colony stimulating factor. Inflammation was observed at vaccine sites clinically for almost all patients, even including ulceration in a subset with each IFA formulation. CD8 T-cell response rates to the 12 melanoma peptides were 53% [95% confidence interval (CI), 44%, 61%)] for IFA-AN and 46% [95% CI, 32%, 59%)] for IFA-VG. In the 93 patient subset, these rates were 73% [95% CI, 61%, 83%)] and 70% [95% CI, 47%, 87%)], respectively. CD4 T-cell responses to tetanus helper peptide were identified in 94% [95% CI, 86%, 98%)] and 96% [95% CI, 78%, 100%)], respectively. Responses to individual human leukocyte antigen (HLA)-A1, A2, and DR associated peptides were largely preserved, but reactivity trended lower for some HLA-A3 associated peptides. Despite the necessarily retrospective nature of the analysis and limitations of multiple comparisons, our summary data support the use of IFA-VG as an adjuvant with multipeptide vaccines in melanoma patients.
authors.affiliation: Department of Surgery/Division of Surgical Oncology, University of Virginia, Charlottesville, VA 22908, USA. cls8h@virginia.edu
authors.forename: Craig L
authors.initials: CL
authors.lastname: Slingluff
authors.forename: Gina R
authors.initials: GR
authors.lastname: Petroni
authors.forename: Mark E
authors.initials: ME
authors.lastname: Smolkin
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Chianese-Bullock
authors.forename: Kelly
authors.initials: K
authors.lastname: Smith
authors.forename: Cheryl
authors.initials: C
authors.lastname: Murphy
authors.forename: Nadedja
authors.initials: N
authors.lastname: Galeassi
authors.forename: Patrice Y
authors.initials: PY
authors.lastname: Neese
authors.forename: William W
authors.initials: WW
authors.lastname: Grosh
authors.forename: Carmel J
authors.initials: CJ
authors.lastname: Nail
authors.forename: Merrick
authors.initials: M
authors.lastname: Ross
authors.forename: Margaret
authors.initials: M
authors.lastname: von Mehren
authors.forename: Naomi
authors.initials: N
authors.lastname: Haas
authors.forename: Marc E
authors.initials: ME
authors.lastname: Boisvert
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019496:Cancer Vaccines; D002417:Cattle; D002478:Cells, Cultured; D005223:Fats / Q000378:metabolism; D005620:Freund's Adjuvant / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D031658:Olea / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology; D022223:Vaccines, Subunit
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D005223:Fats; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D005620:Freund's Adjuvant; C013698:tallow