PMID- 21904219
OWN - NLM
STAT- MEDLINE
DCOM- 20120112
LR  - 20220317
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 34
IP  - 8
DP  - 2011 Oct
TI  - Vaccines targeting the cancer-testis antigen SSX-2 elicit HLA-A2 epitope-specific 
      cytolytic T cells.
PG  - 569-80
LID - 10.1097/CJI.0b013e31822b5b1d [doi]
AB  - The cancer-testis antigen synovial sarcoma X breakpoint-2 (SSX-2) is a 
      potentially attractive target for tumor immunotherapy based upon its 
      tissue-restricted expression to germline cells and its frequent expression in 
      malignancies. The goal of this study was to evaluate genetic vaccine encoding 
      SSX-2 to prioritize human leukocyte antigen (HLA)-A2-specific epitopes and 
      determine if a DNA vaccine can elicit SSX-2-specific cytotoxic T lymphocytes 
      (CTLs) capable of lysing prostate cancer cells. HLA-A2-restricted epitopes were 
      identified based on their in vitro binding affinity for HLA-A2 and by the ability 
      of a genetic vaccine to elicit peptide-specific CTL in A2/DR1 
      (HLA-A2.1+/HLA-DR1+/H-2 class I-/class II-knockout) transgenic mice. We found 
      that SSX-2 peptides p41-49 (KASEKIFYV) and p103-111 (RLQGISPKI) had high affinity 
      for HLA-A2 and were immunogenic in vivo; however, peptide p103-111 was 
      immunodominant with robust peptide-specific immune responses elicited in mice 
      vaccinated with a plasmid DNA vaccine encoding SSX-2. Furthermore, 
      p103-111-specific CTLs were able to lyse an HLA-A2+ prostate cancer cell line. 
      The immunodominance of this epitope was found not to be due to a putative HLA-DR1 
      epitope (p98-112) flanking p103-111. Finally, we demonstrated that SSX-2 
      epitope-specific CTLs could be detected and cultured from the peripheral blood of 
      HLA-A2+ prostate cancer patients, notably patients with advanced prostate cancer. 
      Overall, we conclude that SSX-2 peptide p103-111 is an immunodominant 
      HLA-A2-restricted epitope, and epitope-specific CD8 T cells can be detected in 
      patients with prostate cancer, suggesting that tolerance to SSX-2 can be 
      circumvented in vivo. Together, these findings suggest that SSX-2 may be a 
      relevant target antigen for prostate cancer vaccine approaches.
FAU - Smith, Heath A
AU  - Smith HA
AD  - Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
FAU - McNeel, Douglas G
AU  - McNeel DG
LA  - eng
GR  - T32 CA009135/CA/NCI NIH HHS/United States
GR  - T32 CA009135-33/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (HLA-DR1 Antigen)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Peptides)
RN  - 0 (Repressor Proteins)
RN  - 0 (Vaccines, DNA)
RN  - 164289-47-8 (synovial sarcoma X breakpoint proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cancer Vaccines/*immunology
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Epitopes/*immunology
MH  - HLA-A2 Antigen/*immunology
MH  - HLA-DR1 Antigen/immunology
MH  - Humans
MH  - Leukocytes, Mononuclear/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neoplasm Proteins/*immunology
MH  - Peptides/immunology
MH  - Prostatic Neoplasms/immunology
MH  - Repressor Proteins/*immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Vaccines, DNA/immunology
PMC - PMC3175298
MID - NIHMS315052
COIS- Disclosures: All authors have declared there are no financial conflicts of 
      interest in regards to this work.
EDAT- 2011/09/10 06:00
MHDA- 2012/01/13 06:00
PMCR- 2012/10/01
CRDT- 2011/09/10 06:00
PHST- 2011/09/10 06:00 [entrez]
PHST- 2011/09/10 06:00 [pubmed]
PHST- 2012/01/13 06:00 [medline]
PHST- 2012/10/01 00:00 [pmc-release]
AID - 10.1097/CJI.0b013e31822b5b1d [doi]
PST - ppublish
SO  - J Immunother. 2011 Oct;34(8):569-80. doi: 10.1097/CJI.0b013e31822b5b1d.