PMID- 15542798
OWN - NLM
STAT- MEDLINE
DCOM- 20041208
LR  - 20131121
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 22
IP  - 22
DP  - 2004 Nov 15
TI  - Immunologic and clinical outcomes of vaccination with a multiepitope melanoma 
      peptide vaccine plus low-dose interleukin-2 administered either concurrently or 
      on a delayed schedule.
PG  - 4474-85
AB  - PURPOSE: A phase II trial was performed to test whether systemic low-dose 
      interleukin-2 (IL-2) augments T-cell immune responses to a multipeptide melanoma 
      vaccine. Forty patients with resected stage IIB-IV melanoma were randomly 
      assigned to vaccination with four gp100- and tyrosinase-derived peptides 
      restricted by human leukocyte antigen (HLA) -A1, HLA-A2, and HLA-A3, and a 
      tetanus helper peptide plus IL-2 administered daily either beginning day 7 (group 
      1), or beginning day 28 (group 2). PATIENTS AND METHODS: T-cell responses were 
      assessed by an interferon gamma ELIspot assay in peripheral blood lymphocytes 
      (PBL) and in a lymph node draining a vaccination site (sentinel immunized node 
      [SIN]). Patients were followed for disease-free and overall survival. RESULTS: 
      T-cell responses to the melanoma peptides were observed in 37% of PBL and 38% of 
      SINs in group 1, and in 53% of PBL and 83% of SINs in group 2. The magnitude of 
      T-cell response was higher in group 2. The tyrosinase peptides DAEKSDICTDEY and 
      YMDGTMSQV were more immunogenic than the gp100 peptides YLEPGPVTA and ALLAVGATK. 
      T-cell responses were detected in the SINs more frequently, and with higher 
      magnitude, than responses in the PBL. Disease-free survival estimates at 2 years 
      were 39% (95% CI, 18% to 61%) for group 1, and 50% (95% CI, 28% to 72%) for group 
      2 (P = .32). CONCLUSION: The results of this study support the safety and 
      immunogenicity of a vaccine composed of four peptides derived from gp100 and 
      tyrosinase. The low-dose IL-2 regimen used for group 1 paradoxically diminishes 
      the magnitude and frequency of cytotoxic T lymphocyte responses to these 
      peptides.
FAU - Slingluff, Craig L Jr
AU  - Slingluff CL Jr
AD  - Department of Surgery, Human Immune Therapy Center, University of Virginia Health 
      System, Charlottesville, VA 22908, USA. cls8h@virginia.edu
FAU - Petroni, Gina R
AU  - Petroni GR
FAU - Yamshchikov, Galina V
AU  - Yamshchikov GV
FAU - Hibbitts, Sarah
AU  - Hibbitts S
FAU - Grosh, William W
AU  - Grosh WW
FAU - Chianese-Bullock, Kimberly A
AU  - Chianese-Bullock KA
FAU - Bissonette, Eric A
AU  - Bissonette EA
FAU - Barnd, Donna L
AU  - Barnd DL
FAU - Deacon, Donna H
AU  - Deacon DH
FAU - Patterson, James W
AU  - Patterson JW
FAU - Parekh, Jayashree
AU  - Parekh J
FAU - Neese, Patrice Y
AU  - Neese PY
FAU - Woodson, Elizabeth M H
AU  - Woodson EM
FAU - Wiernasz, Catherine J
AU  - Wiernasz CJ
FAU - Merrill, Priscilla
AU  - Merrill P
LA  - eng
GR  - M01 RR00847/RR/NCRR NIH HHS/United States
GR  - P30 CA44579/CA/NCI NIH HHS/United States
GR  - R01 CA57653/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cancer Vaccines)
RN  - 0 (HLA Antigens)
RN  - 0 (Interleukin-2)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (PMEL protein, human)
RN  - 0 (Vaccines, Subunit)
RN  - 0 (gp100 Melanoma Antigen)
RN  - 42HK56048U (Tyrosine)
SB  - IM
CIN - J Clin Oncol. 2005 Aug 1;23(22):5265-7; author reply 5267-8. PMID: 16051975
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/administration & dosage/*pharmacology
MH  - Cancer Vaccines/administration & dosage/*immunology/*pharmacology
MH  - Disease-Free Survival
MH  - Drug Administration Schedule
MH  - Female
MH  - HLA Antigens/immunology
MH  - Humans
MH  - Interleukin-2/administration & dosage/*pharmacology
MH  - Male
MH  - Melanoma/*drug therapy/*immunology
MH  - Membrane Glycoproteins/immunology
MH  - Middle Aged
MH  - Neoplasm Proteins/immunology
MH  - Skin Neoplasms/*drug therapy/*immunology
MH  - Treatment Outcome
MH  - Tyrosine/immunology
MH  - Vaccines, Subunit/administration & dosage/*immunology/*pharmacology
MH  - gp100 Melanoma Antigen
EDAT- 2004/11/16 09:00
MHDA- 2004/12/16 09:00
CRDT- 2004/11/16 09:00
PHST- 2004/11/16 09:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/11/16 09:00 [entrez]
AID - 22/22/4474 [pii]
AID - 10.1200/JCO.2004.10.212 [doi]
PST - ppublish
SO  - J Clin Oncol. 2004 Nov 15;22(22):4474-85. doi: 10.1200/JCO.2004.10.212.