PMID- 24829756
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140515
LR  - 20211021
IS  - 2051-1426 (Print)
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 1
DP  - 2013
TI  - Immunologic responses to xenogeneic tyrosinase DNA vaccine administered by 
      electroporation in patients with malignant melanoma.
PG  - 20
LID - 10.1186/2051-1426-1-20 [doi]
AB  - BACKGROUND: Prior studies show that intramuscular injection and particle-mediated 
      epidermal delivery of xenogeneic melanosomal antigens (tyrosinase or Tyr, gp100) 
      induce CD8(+) T cell responses to the syngeneic protein. To further define the 
      optimal vaccination strategy, we conducted a phase I study of in vivo 
      electroporation (EP) of a murine Tyr DNA vaccine (pINGmuTyr) in malignant 
      melanoma patients. METHODS: Human leukocyte antigen (HLA)-A1, A2, A24 or B35 
      stage IIb-IV melanoma patients received up to five doses of the mouse tyrosinase 
      DNA vaccine by EP every three weeks at dose levels of 0.2 mg, 0.5 mg, or 1.5 mg 
      per injection. Peripheral blood mononuclear cells (PBMC) were collected, cultured 
      with a peptide pool containing eight HLA class I-restricted Tyr-specific T-cell 
      epitopes, and analyzed by HLA-A*0101-restricted tetramers and intracellular 
      cytokine staining (ICS). RESULTS: Twenty-four patients received >/=1 dose of the 
      pINGmuTyr vaccine; PBMCs from 21 patients who completed all five doses were 
      available for Tyr immune assays. The only common toxicity was grade 1 injection 
      site reaction. Six of 15 patients (40%) in the 1.5 mg dose cohort developed 
      Tyr-reactive CD8(+) T cell responses following stimulation, defined as a >/=3 
      standard deviation increase in baseline reactivity by tetramer or ICS assays. No 
      Tyr-reactive CD8(+) T cell response was detected in the 0.2 mg and 0.5 mg dose 
      cohort patients. Epitope spreading of CD8(+) T cell response to NY-ESO-1 was 
      observed in one patient with vitiligo. One patient subsequently received 
      ipilimumab and developed an enhanced Tyr-reactive response with polyfunctional 
      cytokine profile. After a median follow-up of 40.9 months, median survival has 
      not been reached. CONCLUSIONS: A regimen of five immunizations with pINGmuTyr 
      administered by EP was found to be safe and resulted in Tyr-reactive immune 
      responses in six of 15 patients at 1.5 mg dose cohort. TRIAL REGISTRATION: 
      ClinicalTrials.gov NCT00471133.
FAU - Yuan, Jianda
AU  - Yuan J
AD  - Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering 
      Institute, New York NY10065, USA.
FAU - Ku, Geoffrey Y
AU  - Ku GY
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
FAU - Adamow, Matthew
AU  - Adamow M
AD  - Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering 
      Institute, New York NY10065, USA.
FAU - Mu, Zhenyu
AU  - Mu Z
AD  - Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering 
      Institute, New York NY10065, USA.
FAU - Tandon, Sapna
AU  - Tandon S
AD  - Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering 
      Institute, New York NY10065, USA.
FAU - Hannaman, Drew
AU  - Hannaman D
AD  - Ichor Medical System, Inc., San Diego, CA 92121, USA.
FAU - Chapman, Paul
AU  - Chapman P
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
FAU - Schwartz, Gary
AU  - Schwartz G
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
FAU - Carvajal, Richard
AU  - Carvajal R
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
FAU - Panageas, Katherine S
AU  - Panageas KS
AD  - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer 
      Center, New York NY10065, USA.
FAU - Houghton, Alan N
AU  - Houghton AN
AD  - Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering 
      Institute, New York NY10065, USA.
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
FAU - Wolchok, Jedd D
AU  - Wolchok JD
AD  - Ludwig Center for Cancer Immunotherapy, Immunology Program, Sloan-Kettering 
      Institute, New York NY10065, USA.
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00471133
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20131118
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
PMC - PMC4019903
OTO - NOTNLM
OT  - DNA vaccine
OT  - Electroporation
OT  - Epitope spreading
OT  - Immune response
OT  - Melanoma patient
OT  - Tyrosinase
EDAT- 2013/01/01 00:00
MHDA- 2013/01/01 00:01
PMCR- 2013/11/18
CRDT- 2014/05/16 06:00
PHST- 2013/08/09 00:00 [received]
PHST- 2013/10/31 00:00 [accepted]
PHST- 2014/05/16 06:00 [entrez]
PHST- 2013/01/01 00:00 [pubmed]
PHST- 2013/01/01 00:01 [medline]
PHST- 2013/11/18 00:00 [pmc-release]
AID - 2051-1426-1-20 [pii]
AID - 10.1186/2051-1426-1-20 [doi]
PST - epublish
SO  - J Immunother Cancer. 2013 Nov 18;1:20. doi: 10.1186/2051-1426-1-20. eCollection 
      2013.