Heteroclitic serological response in esophageal and prostate cancer patients after NY-ESO-1 protein vaccination Journal Article


Authors: Kawada, J.; Wada, H.; Isobe, M.; Gnjatic, S.; Nishikawa, H.; Jungbluth, A. A.; Okazaki, N.; Uenaka, A.; Nakamura, Y.; Fujiwara, S.; Mizuno, N.; Saika, T.; Ritter, E.; Yamasaki, M.; Miyata, H.; Ritter, G.; Murphy, R.; Venhaus, R.; Pan, L.; Old, L. J.; Doki, Y.; Nakayama, E.
Article Title: Heteroclitic serological response in esophageal and prostate cancer patients after NY-ESO-1 protein vaccination
Abstract: NY-ESO-1 is a prototypic cancer/testis antigen. In a recent phase I clinical trial, we vaccinated 13 patients bearing NY-ESO-1-expressing tumors with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1) and showed efficient induction of NY-ESO-1 antibody, and CD4 and CD8 T cell responses using peripheral blood from the patients. In our study, we analyzed heteroclitic serological responses in those patients after vaccination. Serological response against 11 tumor antigens including MAGE-A1, MAGE-A3, MAGE-A4, CT7/MAGEC1, CT10/MAGEC2, CT45, CT46/HORMAD1, SOX2, SSX2, XAGE1B and p53 was examined by enzyme-linked immunosorbent assay (ELISA) using sera from ten vaccinated patients. Expression of tumor antigens was determined by reverse transcription-polymerase chain reaction or immunohistochemistry. Eight of nine patients who showed antibody responses against NY-ESO-1 also showed an antibody response against at least 1 of these 11 tumor antigens after vaccination. In one patient, seven tumor antigens were recognized. Specificity analysis of the antibody response by ELISA using control recombinant proteins and synthetic peptides and by Western blot showed that the response was not against His6-tag and/or bacterial products included in a preparation of CHP-NY-ESO-1 used for vaccination. Thus, heteroclitic serological responses appear to be indicative of the overall immune response against the tumor, and their analysis could be useful for immune monitoring in cancer vaccine. Copyright © 2011 UICC.
Keywords: immunohistochemistry; clinical article; protein expression; unclassified drug; clinical trial; cd8+ t lymphocyte; reverse transcription polymerase chain reaction; protein p53; tumor antigen; enzyme linked immunosorbent assay; prostate cancer; immune response; cancer vaccine; cancer testis antigen; melanoma antigen 1; melanoma antigen 3; antibody response; antigen recognition; cancer immunization; cd4+ t lymphocyte; recombinant protein; western blotting; esophagus cancer; transcription factor sox2; bacterium; histidine; melanoma antigen 4; cancer antibody; ny-eso-1; synthetic peptide; ny eso 1 protein; heteroclitic antibody response; ct45 protein; ct46 protein; magec1 protein; magec2 protein; ny eso 1 antibody; ssx2 protein; xage1b protein
Journal Title: International Journal of Cancer
Volume: 130
Issue: 3
ISSN: 0020-7136
Publisher: John Wiley & Sons  
Date Published: 2012-02-01
Start Page: 584
End Page: 592
Language: English
DOI: 10.1002/ijc.26074
PROVIDER: scopus
PUBMED: 21413013
DOI/URL:
Notes: --- - "Export Date: 3 January 2012" - "CODEN: IJCNA" - "Source: Scopus"
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MSK Authors
  1. Sacha Gnjatic
    113 Gnjatic
  2. Achim Jungbluth
    454 Jungbluth
  3. Gerd Ritter
    166 Ritter
  4. Erika Ritter
    37 Ritter
  5. Lloyd J Old
    593 Old