PMID- 20551833
OWN - NLM
STAT- MEDLINE
DCOM- 20101223
LR  - 20211020
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 33
IP  - 6
DP  - 2010 Jul-Aug
TI  - Immunogenicity for CD8+ and CD4+ T cells of 2 formulations of an incomplete 
      freund's adjuvant for multipeptide melanoma vaccines.
PG  - 630-8
LID - 10.1097/CJI.0b013e3181e311ac [doi]
AB  - 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.
FAU - Slingluff, Craig L
AU  - Slingluff CL
AD  - Department of Surgery/Division of Surgical Oncology, University of Virginia, 
      Charlottesville, VA 22908, USA. cls8h@virginia.edu
FAU - Petroni, Gina R
AU  - Petroni GR
FAU - Smolkin, Mark E
AU  - Smolkin ME
FAU - Chianese-Bullock, Kimberly A
AU  - Chianese-Bullock KA
FAU - Smith, Kelly
AU  - Smith K
FAU - Murphy, Cheryl
AU  - Murphy C
FAU - Galeassi, Nadedja
AU  - Galeassi N
FAU - Neese, Patrice Y
AU  - Neese PY
FAU - Grosh, William W
AU  - Grosh WW
FAU - Nail, Carmel J
AU  - Nail CJ
FAU - Ross, Merrick
AU  - Ross M
FAU - von Mehren, Margaret
AU  - von Mehren M
FAU - Haas, Naomi
AU  - Haas N
FAU - Boisvert, Marc E
AU  - Boisvert ME
FAU - Kirkwood, John M
AU  - Kirkwood JM
LA  - eng
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - R01 CA118386-05/CA/NCI NIH HHS/United States
GR  - NIH R01 CA118386/CA/NCI NIH HHS/United States
GR  - R21 CA103528-01/CA/NCI NIH HHS/United States
GR  - P30 CA044579/CA/NCI NIH HHS/United States
GR  - NIH M01 RR00847/RR/NCRR NIH HHS/United States
GR  - R01 CA118386-02/CA/NCI NIH HHS/United States
GR  - R21 CA103528-02/CA/NCI NIH HHS/United States
GR  - P30 CA044579-18/CA/NCI NIH HHS/United States
GR  - R01 CA118386-03/CA/NCI NIH HHS/United States
GR  - R21 CA103528/CA/NCI NIH HHS/United States
GR  - M01 RR000847/RR/NCRR NIH HHS/United States
GR  - NIH R21 CA103528/CA/NCI NIH HHS/United States
GR  - R01 CA118386/CA/NCI NIH HHS/United States
GR  - R01 CA118386-04/CA/NCI NIH HHS/United States
GR  - NIH/NCI P30 CA44579/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Fats)
RN  - 0 (Peptide Fragments)
RN  - 0 (Vaccines, Subunit)
RN  - 9007-81-2 (Freund's Adjuvant)
RN  - 98HPY76U4W (tallow)
SB  - IM
MH  - Adjuvants, Immunologic/*administration & dosage/adverse effects/metabolism
MH  - Animals
MH  - Antigens, Neoplasm/administration & dosage
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism/pathology
MH  - CD8-Positive T-Lymphocytes/immunology/metabolism/pathology
MH  - *Cancer Vaccines
MH  - Cattle
MH  - Cells, Cultured
MH  - Fats/metabolism
MH  - Freund's Adjuvant/*administration & dosage/adverse effects/metabolism
MH  - Humans
MH  - Immunization
MH  - Lymphocyte Activation/drug effects
MH  - Melanoma/*drug therapy/immunology
MH  - Olea/metabolism
MH  - Peptide Fragments/administration & dosage
MH  - Skin Neoplasms/*drug therapy/immunology
MH  - Vaccines, Subunit
PMC - PMC3218563
MID - NIHMS221635
COIS- Financial Disclosure: CLS is listed as an inventor for several peptides used in 
      the melanoma vaccines used in the clinical trials reported in this manuscript, 
      but those patents were filed by the University of Virginia Patent Foundation and 
      have been licensed to Glaxo Smith Kline. All other authors have declared there 
      are no financial conflicts of interest in regards to this work.
EDAT- 2010/06/17 06:00
MHDA- 2010/12/25 06:00
PMCR- 2011/11/17
CRDT- 2010/06/17 06:00
PHST- 2010/06/17 06:00 [entrez]
PHST- 2010/06/17 06:00 [pubmed]
PHST- 2010/12/25 06:00 [medline]
PHST- 2011/11/17 00:00 [pmc-release]
AID - 10.1097/CJI.0b013e3181e311ac [doi]
PST - ppublish
SO  - J Immunother. 2010 Jul-Aug;33(6):630-8. doi: 10.1097/CJI.0b013e3181e311ac.