PMID- 17726460
OWN - NLM
STAT- MEDLINE
DCOM- 20080111
LR  - 20201215
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 15
IP  - 11
DP  - 2007 Nov
TI  - Safety and immunogenicity of tyrosinase DNA vaccines in patients with melanoma.
PG  - 2044-50
AB  - Immunity to self antigens on cancer is constrained by tolerance/ignorance. DNA 
      vaccines encoding xenogeneic differentiation antigens, such as tyrosinase (TYR), 
      mediate tumor protection and regression in implantable mouse models, and dogs 
      with spontaneous melanoma. We conducted a trial of mouse and human TYR DNA 
      vaccines in stage III/IV melanoma patients. Eighteen human leukocyte antigen 
      (HLA)-A*0201(+) melanoma patients were randomized as follows: one group received 
      three mouse TYR DNA injections followed by three human TYR DNA injections; the 
      other group received the same vaccines in opposite sequence. The study was 
      conducted at three dose levels: 100, 500, and 1,500 microg DNA/injection, 
      administered intramuscularly (IM) every 3 weeks. Most toxicities were grade 1 
      injection site reactions. Seven patients developed CD8(+) T-cell responses, 
      defined by a >3 SD increase in baseline reactivity to TYR peptide in tetramer or 
      intracellular cytokine staining (ICS) assays. There was found to be no 
      relationship between dose, assigned schedule, and T-cell response. At a median of 
      42 months follow-up, median survival has not been reached. Mouse and human TYR 
      DNA vaccines were found safe and induced CD8(+) T-cell responses in 7 of 18 
      patients. T cells recognizing a native TYR peptide had a phenotype consistent 
      with that of effector memory cells.
FAU - Wolchok, Jedd D
AU  - Wolchok JD
AD  - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New 
      York 10021, USA. wolchokj@mskcc.org
FAU - Yuan, Jianda
AU  - Yuan J
FAU - Houghton, Alan N
AU  - Houghton AN
FAU - Gallardo, Humilidad F
AU  - Gallardo HF
FAU - Rasalan, Teresa S
AU  - Rasalan TS
FAU - Wang, Jian
AU  - Wang J
FAU - Zhang, Yan
AU  - Zhang Y
FAU - Ranganathan, Rajaram
AU  - Ranganathan R
FAU - Chapman, Paul B
AU  - Chapman PB
FAU - Krown, Susan E
AU  - Krown SE
FAU - Livingston, Philip O
AU  - Livingston PO
FAU - Heywood, Melanie
AU  - Heywood M
FAU - Riviere, Isabelle
AU  - Riviere I
FAU - Panageas, Katherine S
AU  - Panageas KS
FAU - Terzulli, Stephanie L
AU  - Terzulli SL
FAU - Perales, Miguel A
AU  - Perales MA
LA  - eng
GR  - CA008748/CA/NCI NIH HHS/United States
GR  - CA059350/CA/NCI NIH HHS/United States
GR  - CA102606/CA/NCI NIH HHS/United States
GR  - CA33049/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070828
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Antibodies)
RN  - 0 (Vaccines, DNA)
RN  - EC 1.14.18.1 (Monophenol Monooxygenase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Antibodies/immunology
MH  - CD8-Positive T-Lymphocytes/enzymology/immunology
MH  - Drug-Related Side Effects and Adverse Reactions/*immunology
MH  - Humans
MH  - Immunogenetics
MH  - *Immunotherapy
MH  - Melanoma/genetics/*immunology/pathology/*therapy
MH  - Mice
MH  - Middle Aged
MH  - Monophenol Monooxygenase/genetics/*immunology/*metabolism
MH  - Neoplasm Staging
MH  - Phenotype
MH  - Survival Rate
MH  - Vaccines, DNA/administration & dosage/*immunology
EDAT- 2007/08/30 09:00
MHDA- 2008/01/12 09:00
CRDT- 2007/08/30 09:00
PHST- 2007/08/30 09:00 [pubmed]
PHST- 2008/01/12 09:00 [medline]
PHST- 2007/08/30 09:00 [entrez]
AID - S1525-0016(16)32668-5 [pii]
AID - 10.1038/sj.mt.6300290 [doi]
PST - ppublish
SO  - Mol Ther. 2007 Nov;15(11):2044-50. doi: 10.1038/sj.mt.6300290. Epub 2007 Aug 28.