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Frequency of NY-ESO-1 and LAGE-1 expression in bladder cancer and evidence of a new NY-ESO-1 T-cell epitope in a patient with bladder cancer

Padmanee Sharma, Sacha Gnjatic, Achim A. Jungbluth, Barbara Williamson, Harry Herr, Elisabeth Stockert, Guido Dalbagni, S. Machele Donat, Victor E. Reuter, Darren Santiago, Yao-Tseng Chen, Dean F. Bajorin, Gerd Ritter and Lloyd J. Old
Padmanee Sharma
1Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, USA
2Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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Sacha Gnjatic
1Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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Achim A. Jungbluth
1Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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Barbara Williamson
1Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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Harry Herr
3Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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Elisabeth Stockert
1Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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Guido Dalbagni
3Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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S. Machele Donat
3Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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Victor E. Reuter
4Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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Darren Santiago
1Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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Yao-Tseng Chen
5Department of Pathology, Weill Medical College of Cornell University, New York, NY, USA
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Dean F. Bajorin
2Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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Gerd Ritter
1Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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Lloyd J. Old
1Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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DOI:  Published January 2003
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    Figure 1

    Summary of NY-ESO-1 and LAGE-1 expression in TCCs as determined by IHC and RT-PCR

  • Figure 2
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    Figure 2

    Recurrence-free survival in patients whose tumors expressed antigen (NY-ESO-1 or LAGE-1) versus patients whose tumors did not express antigen

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    Figure 3

    Antibodies to NY-ESO-1 in patient UC-098 at various time points. Antibodies to NY-ESO-1 at 8 , 10 and 22 months after cystectomy are shown, as compared to a known positive control and negative control.

  • Figure 4
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    Figure 4

    Expression of NY-ESO-1 in patient UC-098 with invasive transitional cell carcinoma. Homogeneous expression of NY-ESO-1 in urinary bladder was detected with monoclonal antibody ES121.

  • Figure 5
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    Figure 5

    Mapping of the epitope within region 80-109 of NY-ESO-1. ELISPOT assay with CD8+ T cells from patient UC-098 presensitized with NY-ESO-1 peptide 80-109 and tested against histocompatible B-EBV targets pulsed with peptides at 10 µM (A and B) or at various concentrations (C).

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    Figure 6

    Identification of the restriction element responsible for the observed T cell response. ELISPOT assay with CD8+ T cells from patient UC-098 presensitized with NY-ESO-1 peptide 80-109 and tested against partially histocompatible B-EBV targets pulsed or not with NY-ESO-1 peptide 94-102. The complete class I haplotype from UC-098 is indicated on top, matching target alleles are shown in bold and italic print.

  • Figure 7
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    Figure 7

    NY-ESO-1 peptide 94-102 is naturally processed from the full-length protein in antigen-presenting cells. ELISPOT assay with CD8+ T cells from patient UC-098 presensitized with NY-ESO-1 peptide 80-109 and tested against histocompatible B-EBV targets pulsed with NY-ESO-1 peptides, or infected with vaccinia virus recombinant for NY-ESO-1 or wild-type (A); or tested against melanoma cell lines pulsed or not with NY-ESO-1 peptide 94-102 (B).

Tables

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  • Table 1

    RT-PCR and IHC results from high-grade TCCs.

    Patient Number Pathology IHC RT-PCR
    NY-ESO-1 NY-ESO-1 LAGE-1
    UC014 TaG1 + CIS not tested - +
    UC032 T2 + CIS not tested - +
    UC033 T1 - - -
    UC037 T4 + + +
    UC040 T1 +CIS - - -
    UC041 T2 - - -
    UC060 T2 - + +
    UC061 T2 + CIS + + +
    UC063 CIS not tested + -
    UC067 T3 - + +
    UC070 T1 + CIS - - -
    UC081 T2 - - -
    UC095 CIS not tested - -
    UC099 Ta-high grade - + -
    UC101 T2 + CIS - - -
    UC106 Ta-high grade - + +
    UC113 CIS - + +
    UC114 T1 - + -
    UC117 Ta-high grade - - +
    UC121 Ta-high grade not tested - -
    UC124 T1 - + -
    UC128 T2 - - -
    UC131 CIS - - -
    UC139 T2 not tested - -
    UC141 T1 not tested - -
    UC143 T2 + CIS - - +
    UC144 T2 - - -
    UC146 T2 - - +
    UC148 T1 - + +
    UC149 T2 - - -
    UC150 T1 - - +
    UC155 CIS not tested - -
    UC160 T2 + - -
    UC161 T2 - - -
    UC164 T3 - - +
    UC165 CIS not tested - -
    UC166 T3 + CIS - - -
    UC169 T2 + CIS not tested - -
    UC170 T3 + CIS + + +
    UC201 T3 + CIS + + +
    UC202 T3 + + -
    UC203 T3 + CIS - - -
    UC204 T3 - + +
  • Table 2

    Characteristics of the patients included in the statistical analysis.

    Pathology N (%)
    CIS 12 (17)
    T1 11 (16)
    T1 + CIS 3 (4)
    T2 9 (13)
    T2 + CIS 4 (6)
    T3 7 (10)
    T3 + CIS 7 (10)
    T4 3 (4)
    TaG1 + CIS 2 (3)
    TaG3 10 (15)
    TaG3 + CIS 1 (2)
    Diagnosis Dates
    Starting 6/97
    Ending 11/02
    Survival Status N (%)
    Alive 61 (88)
    Dead 8 (12)
    Antigen Results N
    Positive (for at least 1) 33
    Negative 36
  • Table 3

    Summary of recurrence-free survival (RFS) for 69 patients with high-grade TCC.

    RFS All Patients Ag Negative Patients Ag Positive Patients
    Median RFS (95% CI) 24.4 mo (15.8, 70.2) 24.4 mo (17.9, 70.2) Not reached
    One-year RFS (95% CI) 68% (57, 79) 69% (54, 85) 67% (50, 83)
    Two-year RFS (95% CI) 51% (38, 64) 51% (33, 69) 52% (34, 70)
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Cancer Immunity Archive: 3 (1)
January 2003
Volume 3, Issue 1
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Frequency of NY-ESO-1 and LAGE-1 expression in bladder cancer and evidence of a new NY-ESO-1 T-cell epitope in a patient with bladder cancer
Padmanee Sharma, Sacha Gnjatic, Achim A. Jungbluth, Barbara Williamson, Harry Herr, Elisabeth Stockert, Guido Dalbagni, S. Machele Donat, Victor E. Reuter, Darren Santiago, Yao-Tseng Chen, Dean F. Bajorin, Gerd Ritter and Lloyd J. Old
Cancer Immun January 1 2003 (3) (1) 19;

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Frequency of NY-ESO-1 and LAGE-1 expression in bladder cancer and evidence of a new NY-ESO-1 T-cell epitope in a patient with bladder cancer
Padmanee Sharma, Sacha Gnjatic, Achim A. Jungbluth, Barbara Williamson, Harry Herr, Elisabeth Stockert, Guido Dalbagni, S. Machele Donat, Victor E. Reuter, Darren Santiago, Yao-Tseng Chen, Dean F. Bajorin, Gerd Ritter and Lloyd J. Old
Cancer Immun January 1 2003 (3) (1) 19;
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