PMID- 19924797
OWN - NLM
STAT- MEDLINE
DCOM- 20100309
LR  - 20141120
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 116
IP  - 2
DP  - 2010 Jan 15
TI  - Results of the first phase 1 clinical trial of the HER-2/neu peptide (GP2) 
      vaccine in disease-free breast cancer patients: United States Military Cancer 
      Institute Clinical Trials Group Study I-04.
PG  - 292-301
LID - 10.1002/cncr.24756 [doi]
AB  - BACKGROUND: HER-2/neu, overexpressed in breast cancer, is a source of immunogenic 
      peptides that include GP2 and E75. Phase 2 testing of E75 as an adjuvant vaccine 
      has suggested a clinical benefit. GP2, derived from the transmembrane portion of 
      HER-2/neu, has differing binding characteristics and may be more immunogenic than 
      E75. Results of the first phase 1 trial of GP2 peptide vaccine are presented. 
      METHODS: Disease-free, lymph node-negative, human leukocyte antigen (HLA)-A2(+) 
      breast cancer patients were enrolled. This dose escalation trial included 4 
      groups to determine safety and optimal GP2 peptide/granulocyte-macrophage 
      colony-stimulating factor (GM-CSF) dose. Toxicities were monitored. Immunologic 
      response was assessed ex vivo via the HLA-A2:immunoglobulin dimer assay to detect 
      GP2-specific CD8(+) T cells (and E75-specific CD8(+) T cells to assess epitope 
      spreading) and in vivo via delayed type hypersensitivity (DTH) reaction 
      (medians/ranges). RESULTS: Eighteen patients were enrolled. All toxicities were 
      grade < or =2. Eight (88.9%) of 9 patients in the first 3 dose groups required 
      GM-CSF dose reductions for local reactions > or =100 mm or grade > or =2 systemic 
      toxicity. GM-CSF dose was reduced to 125 microg for the final dose group. All 
      patients responded immunologically ex vivo (GP2-specific CD8(+) T cells from 
      prevaccination to maximum, 0.4% [0.0%-2.0%] to 1.1% [0.4%-3.6%], P < .001) and in 
      vivo (GP2 pre- to postvaccination DTH, 0 mm [0.0-19.5 mm] to 27.5 mm [0.0-114.5 
      mm, P < .001). E75-specific CD8(+) T cells also increased in response to GP2 from 
      prevaccination to maximum (0.8% [0.0%-2.41%] to 1.6% [0.86%-3.72%], P < .001). 
      CONCLUSIONS: The GP2 peptide vaccine appears safe and well tolerated with minimal 
      local/systemic toxicity. GP2 elicited HER-2/neu-specific immune responses, 
      including epitope spreading, in high-risk, lymph node-negative breast cancer 
      patients. These findings support further investigation of the GP2 vaccine for the 
      prevention of breast cancer recurrence.
FAU - Carmichael, Mark G
AU  - Carmichael MG
AD  - Cancer Vaccine Development Program, United States Military Cancer Institute, 
      Department of Surgery, Uniformed Services University of the Health Sciences, 
      Bethesda, Maryland, USA.
FAU - Benavides, Linda C
AU  - Benavides LC
FAU - Holmes, Jarrod P
AU  - Holmes JP
FAU - Gates, Jeremy D
AU  - Gates JD
FAU - Mittendorf, Elizabeth A
AU  - Mittendorf EA
FAU - Ponniah, Sathibalan
AU  - Ponniah S
FAU - Peoples, George E
AU  - Peoples GE
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes)
RN  - 0 (HER2-neu-derived peptide (654-662))
RN  - 0 (Peptide Fragments)
RN  - 0 (Vaccines, Subunit)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Breast Neoplasms/*therapy
MH  - Cancer Vaccines/adverse effects/immunology/*therapeutic use
MH  - Epitopes/analysis
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage
MH  - Humans
MH  - Middle Aged
MH  - Peptide Fragments/*immunology
MH  - Receptor, ErbB-2/*immunology
MH  - Vaccines, Subunit/adverse effects/immunology/therapeutic use
EDAT- 2009/11/20 06:00
MHDA- 2010/03/10 06:00
CRDT- 2009/11/20 06:00
PHST- 2009/11/20 06:00 [entrez]
PHST- 2009/11/20 06:00 [pubmed]
PHST- 2010/03/10 06:00 [medline]
AID - 10.1002/cncr.24756 [doi]
PST - ppublish
SO  - Cancer. 2010 Jan 15;116(2):292-301. doi: 10.1002/cncr.24756.