PMID- 21697278
OWN - NLM
STAT- MEDLINE
DCOM- 20111013
LR  - 20121115
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 71
IP  - 16
DP  - 2011 Aug 15
TI  - A novel tumor antigen derived from enhanced degradation of bax protein in human 
      cancers.
PG  - 5435-44
LID - 10.1158/0008-5472.CAN-11-0393 [doi]
AB  - Cancer cells frequently exhibit defects in apoptosis, which contribute to 
      increased survival and chemotherapeutic resistance. For example, genetic 
      mutations or abnormal proteasomal degradation can reduce expression of Bax which 
      limits apoptosis. In cancers where abnormal proteasomal degradation of Bax 
      occurs, we hypothesized that Bax peptides that bind to human leukocyte antigen 
      (HLA) class I molecules would be generated for presentation to CD8(+) T cells. To 
      test this hypothesis, we generated T cells against pooled Bax peptides, using the 
      blood of healthy human donors. Although T-cell responses were of low frequency 
      (0.15%), a CD8(+) T-cell clone (KSIVB17) was isolated that optimally recognized 
      Bax(136-144) peptide (IMGWTLDFL) presented by HLA-A*0201. KSIVB17 was able to 
      recognize and kill a variety of HLA-matched cancer cells including primary tumor 
      cells from chronic lymphocytic leukemia (CLL). No reactivity was seen against 
      HLA-matched, nontransformed cells such as PHA blasts and skin fibroblasts. 
      Furthermore, KSIVB17 reactivity corresponded with the proteasomal degradation 
      patterns of Bax protein observed in cancer cells. Taken together, our findings 
      suggest a new concept for tumor antigens based on regulatory proteins that are 
      ubiquitously expressed in normal cells, but that have abnormally enhanced 
      degradation in cancer cells. Bax degradation products offer candidate immune 
      antigens in cancers such as CLL in which increased Bax degradation correlates 
      with poor clinical prognosis.
FAU - Nunes, Claudia Trindade
AU  - Nunes CT
AD  - Departments of Infection, Immunity and Biochemistry, School of Medicine, Cardiff 
      University, Cardiff, Wales, United Kingdom.
FAU - Miners, Kelly L
AU  - Miners KL
FAU - Dolton, Garry
AU  - Dolton G
FAU - Pepper, Chris
AU  - Pepper C
FAU - Fegan, Chris
AU  - Fegan C
FAU - Mason, Malcolm D
AU  - Mason MD
FAU - Man, Stephen
AU  - Man S
LA  - eng
PT  - Journal Article
DEP - 20110622
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (bcl-2-Associated X Protein)
SB  - IM
MH  - Antigens, Neoplasm/*isolation & purification
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Histocompatibility Antigens Class I/immunology
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*immunology
MH  - Proteasome Inhibitors
MH  - bcl-2-Associated X Protein/chemistry/*metabolism
EDAT- 2011/06/24 06:00
MHDA- 2011/10/14 06:00
CRDT- 2011/06/24 06:00
PHST- 2011/06/24 06:00 [entrez]
PHST- 2011/06/24 06:00 [pubmed]
PHST- 2011/10/14 06:00 [medline]
AID - 0008-5472.CAN-11-0393 [pii]
AID - 10.1158/0008-5472.CAN-11-0393 [doi]
PST - ppublish
SO  - Cancer Res. 2011 Aug 15;71(16):5435-44. doi: 10.1158/0008-5472.CAN-11-0393. Epub 
      2011 Jun 22.