PMID- 18567615
OWN - NLM
STAT- MEDLINE
DCOM- 20090619
LR  - 20211203
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 20
IP  - 8
DP  - 2008 Aug
TI  - Identification and functional validation of MHC class I epitopes in the 
      tumor-associated antigen 5T4.
PG  - 1057-66
LID - 10.1093/intimm/dxn063 [doi]
AB  - The cancer vaccine TroVax, modified vaccinia Ankara encoding the tumor-associated 
      antigen 5T4, has been tested in phase I and II studies in colorectal cancer 
      patients. Monitoring of 5T4-specific immune responses in patients receiving 
      TroVax is critical since it could inform future refinements to the therapeutic or 
      provide a surrogate marker of clinical efficacy. Tumor-specific cytotoxic T 
      lymphocyte (CTL) are considered to be a key component of an effective anti-cancer 
      immune response. Though numerous techniques have been employed to identify CTL 
      epitopes, many are labor intensive, of variable reliability or biased toward 
      common alleles such as human leukocyte antigen (HLA)-A2. A new high-throughput 
      technique, iTopia, enables peptides to be evaluated on the basis of their 
      physical binding properties for HLA alleles. This technique has been utilized to 
      rapidly screen a panel of overlapping peptides, spanning the length of 5T4. 
      Initially, peptides which bound to four class I alleles (A*0101, A*0201, A*0301 
      and B*0702) were identified and their physical binding characteristics assessed 
      further by analysis of relative affinity and complex stability. 46 putative CTL 
      epitopes have been identified which bind to at least one of the four HLA alleles. 
      Using PBMCs from patients vaccinated with TroVax, we have used the interferon 
      gamma (IFN gamma) ELISpot assay to validate one predicted A1 and two A2 epitopes. 
      CONCLUSION: iTopia represents a rapid and high-throughput technique to identify 
      CTL epitopes.
FAU - Shingler, William H
AU  - Shingler WH
AD  - Oxford BioMedica (UK) Ltd, Medawar Centre, Oxford Science Park, Oxford, OX4 4GA, 
      UK. w.shingler@oxfordbiomedica.co.uk
FAU - Chikoti, Priscilla
AU  - Chikoti P
FAU - Kingsman, Susan M
AU  - Kingsman SM
FAU - Harrop, Richard
AU  - Harrop R
LA  - eng
PT  - Journal Article
DEP - 20080620
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Peptides)
RN  - 0 (TroVax)
RN  - 0 (Vaccines, DNA)
RN  - 0 (trophoblastic glycoprotein 5T4, human)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antigens, Neoplasm/chemistry/*immunology/metabolism
MH  - Cancer Vaccines/*immunology
MH  - Colorectal Neoplasms/*immunology/pathology/therapy
MH  - Epitope Mapping
MH  - Epitopes, T-Lymphocyte/chemistry/*immunology/metabolism
MH  - HLA-A Antigens/chemistry/metabolism
MH  - HLA-B Antigens/chemistry/metabolism
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Lymphocyte Activation/drug effects/immunology
MH  - Membrane Glycoproteins/chemistry/*immunology/metabolism
MH  - Neoplasms, Glandular and Epithelial/*immunology/pathology/therapy
MH  - Peptides/chemistry/immunology/therapeutic use
MH  - Protein Binding
MH  - T-Lymphocytes, Cytotoxic/immunology/*metabolism/pathology
MH  - Vaccines, DNA
EDAT- 2008/06/24 09:00
MHDA- 2009/06/20 09:00
CRDT- 2008/06/24 09:00
PHST- 2008/06/24 09:00 [pubmed]
PHST- 2009/06/20 09:00 [medline]
PHST- 2008/06/24 09:00 [entrez]
AID - dxn063 [pii]
AID - 10.1093/intimm/dxn063 [doi]
PST - ppublish
SO  - Int Immunol. 2008 Aug;20(8):1057-66. doi: 10.1093/intimm/dxn063. Epub 2008 Jun 
      20.