PMID- 20647477
OWN - NLM
STAT- MEDLINE
DCOM- 20101115
LR  - 20211203
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 16
IP  - 15
DP  - 2010 Aug 1
TI  - Immunologic response to xenogeneic gp100 DNA in melanoma patients: comparison of 
      particle-mediated epidermal delivery with intramuscular injection.
PG  - 4057-65
LID - 10.1158/1078-0432.CCR-10-1093 [doi]
AB  - PURPOSE: Prior studies show that i.m. injection of xenogeneic orthologues of 
      melanosomal antigens (tyrosinase, gp100) induces CD8(+) T-cell responses to the 
      syngeneic protein. To further define the optimal vaccination strategy, we 
      conducted a pilot clinical trial comparing i.m. injection with particle-mediated 
      epidermal delivery (PMED). EXPERIMENTAL DESIGN: Human leukocyte antigen 
      (HLA)-A*0201(+) disease-free melanoma patients were randomized to the PMED or 
      i.m. arm, receiving eight vaccinations over 4 months. Patients received 4 microg 
      or 2,000 microg per injection, respectively, of mouse gp100 DNA. Peripheral blood 
      mononuclear cells were collected, cultured with gp100 peptides, and analyzed by 
      tetramer and intracellular cytokine staining for responses to 
      HLA-A*0201-restricted gp100 epitopes [gp100(209-217) (ITDQVPFSV) and 
      gp100(280-288) (YLEPGPVTA)]. RESULTS: Twenty-seven patients with stage IIB-IV 
      melanoma were analyzable for immune response. The only common toxicity was grade 
      1 injection site reaction in nine patients with no intergroup difference, and one 
      dose-limiting toxicity of acute hypersensitivity occurred in a PMED patient with 
      undiagnosed gold allergy. Four of 27 patients produced gp100 tetramer(+)CD8(+) T 
      cells, all carrying the CCR7(lo)CD45RA(lo) effector-memory phenotype. Five of 27 
      patients generated IFN-gamma(+)CD8(+) T cells, one who was also 
      tetramer-positive. Overall, vaccination induced a response in 30% of patients, 
      which was not significantly associated with study arm or clinical outcome. 
      However, the PMED group showed a trend toward increased IFN-gamma(+)CD8(+) T-cell 
      generation (P = 0.07). CONCLUSION: A comparable efficacy and safety profile was 
      shown between the i.m. and PMED arms, despite a significantly decreased dose of 
      DNA used for PMED injection.
CI  - (c) 2010 AACR.
FAU - Ginsberg, Brian A
AU  - Ginsberg BA
AD  - Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering 
      Institute, 1275 York Avenue, New York, NY 10065, USA.
FAU - Gallardo, Humilidad F
AU  - Gallardo HF
FAU - Rasalan, Teresa S
AU  - Rasalan TS
FAU - Adamow, Matthew
AU  - Adamow M
FAU - Mu, Zhenyu
AU  - Mu Z
FAU - Tandon, Sapna
AU  - Tandon S
FAU - Bewkes, Barrett B
AU  - Bewkes BB
FAU - Roman, Ruth-Ann
AU  - Roman RA
FAU - Chapman, Paul B
AU  - Chapman PB
FAU - Schwartz, Gary K
AU  - Schwartz GK
FAU - Carvajal, Richard D
AU  - Carvajal RD
FAU - Panageas, Katherine S
AU  - Panageas KS
FAU - Terzulli, Stephanie L
AU  - Terzulli SL
FAU - Houghton, Alan N
AU  - Houghton AN
FAU - Yuan, Jianda D
AU  - Yuan JD
FAU - Wolchok, Jedd D
AU  - Wolchok JD
LA  - eng
GR  - R25 CA020449/CA/NCI NIH HHS/United States
GR  - P01CA33049/CA/NCI NIH HHS/United States
GR  - P01 CA033049/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R01 CA056821/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100720
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antigens, Heterophile)
RN  - 0 (Cancer Vaccines)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (PMEL protein, human)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (Pmel protein, mouse)
RN  - 0 (Vaccines, DNA)
RN  - 0 (gp100 Melanoma Antigen)
RN  - 0 (gp100(280-288) melanoma antigen peptide)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Administration, Intranasal
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Antigens, Heterophile/administration & dosage/adverse effects
MH  - *Biolistics
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cancer Vaccines/*administration & dosage/adverse effects/*immunology
MH  - DNA/administration & dosage/adverse effects/immunology
MH  - Female
MH  - HLA-A Antigens
MH  - HLA-A2 Antigen
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Melanoma/mortality/pathology/*therapy
MH  - Membrane Glycoproteins/*administration & dosage/adverse effects/immunology
MH  - Mice
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Peptide Fragments
MH  - Peptides
MH  - Pilot Projects
MH  - Vaccines, DNA/administration & dosage/adverse effects/immunology
MH  - gp100 Melanoma Antigen
PMC - PMC4241567
MID - NIHMS215758
EDAT- 2010/07/22 06:00
MHDA- 2010/11/16 06:00
PMCR- 2014/11/24
CRDT- 2010/07/22 06:00
PHST- 2010/07/22 06:00 [entrez]
PHST- 2010/07/22 06:00 [pubmed]
PHST- 2010/11/16 06:00 [medline]
PHST- 2014/11/24 00:00 [pmc-release]
AID - 1078-0432.CCR-10-1093 [pii]
AID - 10.1158/1078-0432.CCR-10-1093 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2010 Aug 1;16(15):4057-65. doi: 10.1158/1078-0432.CCR-10-1093. 
      Epub 2010 Jul 20.