Immunogenicity for CD8+ and CD4+ T cells of 2 formulations of an incomplete freund's adjuvant for multipeptide melanoma vaccines.
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.
Slingluff
Craig L
CL
Department of Surgery/Division of Surgical Oncology, University of Virginia, Charlottesville, VA 22908, USA. cls8h@virginia.edu
Petroni
Gina R
GR
Smolkin
Mark E
ME
Chianese-Bullock
Kimberly A
KA
Smith
Kelly
K
Murphy
Cheryl
C
Galeassi
Nadedja
N
Neese
Patrice Y
PY
Grosh
William W
WW
Nail
Carmel J
CJ
Ross
Merrick
M
von Mehren
Margaret
M
Haas
Naomi
N
Boisvert
Marc E
ME
Kirkwood
John M
JM
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
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D005223:Fats; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D005620:Freund's Adjuvant; C013698:tallow