NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma

Seth M. Pollack, Achim A. Jungbluth, Benjamin L. Hoch, Erik A. Farrar, Marie Bleakley, David J. Schneider, Elizabeth T. Loggers, Eve Rodler, Janet F. Eary, Ernest U. Conrad, Robin L. Jones, Cassian Yee

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

BACKGROUND: Myxoid/round cell liposarcoma (MRCL) is the second most common liposarcoma subtype, accounting for >33% of liposarcomas and approximately 10% of all soft tissue sarcomas. Although MRCL is a chemosensitive subtype, patients with metastatic disease have a poor outcome. NY-ESO-1 is a cancer-testis antigen (also known as cancer germ cell antigen) that has been successfully targeted in vaccine trials and in adoptive T-cell therapy trials for the treatment of several solid tumors. METHODS: The authors investigated the feasibility of targeting NY-ESO-1 in patients with MRCL by evaluating the prevalence of NY-ESO-1 expression in tumors using immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction analysis. NY-ESO-1-specific tumor recognition by NY-ESO-1-specific T-cells also was analyzed using a chromium release assay. RESULTS: A search of the University of Washington Sarcoma Tissue Bank identified paraffin-embedded tumor samples from 25 patients with MRCL. NY-ESO-1 expression was observed in every MRCL tumor assessed (100%); in 18 tumors (72%), staining was homogenous. In all but 2 tumors, staining was sufficiently robust (2+) that such patients would be eligible for clinical trials of NY-ESO-1-directed therapy. By using NY-ESO-1 specific, CD8-positive T-cells, the in vitro sensitivity of myxoid liposarcoma cell lines to antigen-specific lysis was demonstrated. CONCLUSIONS: The current results establish NY-ESO-1 as an important target antigen for the treatment of patients with MRCL. Cancer 2012. © 2012 American Cancer Society. The authors demonstrate that the cancer-testis antigen NY-ESO-1 is expressed in 100% of myxoid/round cell liposarcoma (MRCL) tumors tested and that MRCL cell lines can be recognized and specifically lysed by NY-ESO-1-specific effectors in vitro. These results establish NY-ESO-1 as an important target antigen for the treatment of patients with MRCL.

Original languageEnglish (US)
Pages (from-to)4564-4570
Number of pages7
JournalCancer
Volume118
Issue number18
DOIs
StatePublished - Sep 15 2012
Externally publishedYes

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Liposarcoma
Antigens
Neoplasms
Testicular Neoplasms
T-Lymphocytes
Sarcoma
Myxoid Liposarcoma
Tissue Banks
Staining and Labeling
Cell Line
Germ Cell and Embryonal Neoplasms
Chromium
Therapeutics
Cell- and Tissue-Based Therapy
Reverse Transcriptase Polymerase Chain Reaction
Paraffin
Vaccines
Immunohistochemistry
Clinical Trials

Keywords

  • cancer testis antigens
  • immunotherapy
  • myxoid
  • NY-ESO-1
  • sarcoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pollack, S. M., Jungbluth, A. A., Hoch, B. L., Farrar, E. A., Bleakley, M., Schneider, D. J., ... Yee, C. (2012). NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma. Cancer, 118(18), 4564-4570. https://doi.org/10.1002/cncr.27446

NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma. / Pollack, Seth M.; Jungbluth, Achim A.; Hoch, Benjamin L.; Farrar, Erik A.; Bleakley, Marie; Schneider, David J.; Loggers, Elizabeth T.; Rodler, Eve; Eary, Janet F.; Conrad, Ernest U.; Jones, Robin L.; Yee, Cassian.

In: Cancer, Vol. 118, No. 18, 15.09.2012, p. 4564-4570.

Research output: Contribution to journalArticle

Pollack, SM, Jungbluth, AA, Hoch, BL, Farrar, EA, Bleakley, M, Schneider, DJ, Loggers, ET, Rodler, E, Eary, JF, Conrad, EU, Jones, RL & Yee, C 2012, 'NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma', Cancer, vol. 118, no. 18, pp. 4564-4570. https://doi.org/10.1002/cncr.27446
Pollack SM, Jungbluth AA, Hoch BL, Farrar EA, Bleakley M, Schneider DJ et al. NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma. Cancer. 2012 Sep 15;118(18):4564-4570. https://doi.org/10.1002/cncr.27446
Pollack, Seth M. ; Jungbluth, Achim A. ; Hoch, Benjamin L. ; Farrar, Erik A. ; Bleakley, Marie ; Schneider, David J. ; Loggers, Elizabeth T. ; Rodler, Eve ; Eary, Janet F. ; Conrad, Ernest U. ; Jones, Robin L. ; Yee, Cassian. / NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma. In: Cancer. 2012 ; Vol. 118, No. 18. pp. 4564-4570.
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abstract = "BACKGROUND: Myxoid/round cell liposarcoma (MRCL) is the second most common liposarcoma subtype, accounting for >33{\%} of liposarcomas and approximately 10{\%} of all soft tissue sarcomas. Although MRCL is a chemosensitive subtype, patients with metastatic disease have a poor outcome. NY-ESO-1 is a cancer-testis antigen (also known as cancer germ cell antigen) that has been successfully targeted in vaccine trials and in adoptive T-cell therapy trials for the treatment of several solid tumors. METHODS: The authors investigated the feasibility of targeting NY-ESO-1 in patients with MRCL by evaluating the prevalence of NY-ESO-1 expression in tumors using immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction analysis. NY-ESO-1-specific tumor recognition by NY-ESO-1-specific T-cells also was analyzed using a chromium release assay. RESULTS: A search of the University of Washington Sarcoma Tissue Bank identified paraffin-embedded tumor samples from 25 patients with MRCL. NY-ESO-1 expression was observed in every MRCL tumor assessed (100{\%}); in 18 tumors (72{\%}), staining was homogenous. In all but 2 tumors, staining was sufficiently robust (2+) that such patients would be eligible for clinical trials of NY-ESO-1-directed therapy. By using NY-ESO-1 specific, CD8-positive T-cells, the in vitro sensitivity of myxoid liposarcoma cell lines to antigen-specific lysis was demonstrated. CONCLUSIONS: The current results establish NY-ESO-1 as an important target antigen for the treatment of patients with MRCL. Cancer 2012. {\circledC} 2012 American Cancer Society. The authors demonstrate that the cancer-testis antigen NY-ESO-1 is expressed in 100{\%} of myxoid/round cell liposarcoma (MRCL) tumors tested and that MRCL cell lines can be recognized and specifically lysed by NY-ESO-1-specific effectors in vitro. These results establish NY-ESO-1 as an important target antigen for the treatment of patients with MRCL.",
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AU - Pollack, Seth M.

AU - Jungbluth, Achim A.

AU - Hoch, Benjamin L.

AU - Farrar, Erik A.

AU - Bleakley, Marie

AU - Schneider, David J.

AU - Loggers, Elizabeth T.

AU - Rodler, Eve

AU - Eary, Janet F.

AU - Conrad, Ernest U.

AU - Jones, Robin L.

AU - Yee, Cassian

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N2 - BACKGROUND: Myxoid/round cell liposarcoma (MRCL) is the second most common liposarcoma subtype, accounting for >33% of liposarcomas and approximately 10% of all soft tissue sarcomas. Although MRCL is a chemosensitive subtype, patients with metastatic disease have a poor outcome. NY-ESO-1 is a cancer-testis antigen (also known as cancer germ cell antigen) that has been successfully targeted in vaccine trials and in adoptive T-cell therapy trials for the treatment of several solid tumors. METHODS: The authors investigated the feasibility of targeting NY-ESO-1 in patients with MRCL by evaluating the prevalence of NY-ESO-1 expression in tumors using immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction analysis. NY-ESO-1-specific tumor recognition by NY-ESO-1-specific T-cells also was analyzed using a chromium release assay. RESULTS: A search of the University of Washington Sarcoma Tissue Bank identified paraffin-embedded tumor samples from 25 patients with MRCL. NY-ESO-1 expression was observed in every MRCL tumor assessed (100%); in 18 tumors (72%), staining was homogenous. In all but 2 tumors, staining was sufficiently robust (2+) that such patients would be eligible for clinical trials of NY-ESO-1-directed therapy. By using NY-ESO-1 specific, CD8-positive T-cells, the in vitro sensitivity of myxoid liposarcoma cell lines to antigen-specific lysis was demonstrated. CONCLUSIONS: The current results establish NY-ESO-1 as an important target antigen for the treatment of patients with MRCL. Cancer 2012. © 2012 American Cancer Society. The authors demonstrate that the cancer-testis antigen NY-ESO-1 is expressed in 100% of myxoid/round cell liposarcoma (MRCL) tumors tested and that MRCL cell lines can be recognized and specifically lysed by NY-ESO-1-specific effectors in vitro. These results establish NY-ESO-1 as an important target antigen for the treatment of patients with MRCL.

AB - BACKGROUND: Myxoid/round cell liposarcoma (MRCL) is the second most common liposarcoma subtype, accounting for >33% of liposarcomas and approximately 10% of all soft tissue sarcomas. Although MRCL is a chemosensitive subtype, patients with metastatic disease have a poor outcome. NY-ESO-1 is a cancer-testis antigen (also known as cancer germ cell antigen) that has been successfully targeted in vaccine trials and in adoptive T-cell therapy trials for the treatment of several solid tumors. METHODS: The authors investigated the feasibility of targeting NY-ESO-1 in patients with MRCL by evaluating the prevalence of NY-ESO-1 expression in tumors using immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction analysis. NY-ESO-1-specific tumor recognition by NY-ESO-1-specific T-cells also was analyzed using a chromium release assay. RESULTS: A search of the University of Washington Sarcoma Tissue Bank identified paraffin-embedded tumor samples from 25 patients with MRCL. NY-ESO-1 expression was observed in every MRCL tumor assessed (100%); in 18 tumors (72%), staining was homogenous. In all but 2 tumors, staining was sufficiently robust (2+) that such patients would be eligible for clinical trials of NY-ESO-1-directed therapy. By using NY-ESO-1 specific, CD8-positive T-cells, the in vitro sensitivity of myxoid liposarcoma cell lines to antigen-specific lysis was demonstrated. CONCLUSIONS: The current results establish NY-ESO-1 as an important target antigen for the treatment of patients with MRCL. Cancer 2012. © 2012 American Cancer Society. The authors demonstrate that the cancer-testis antigen NY-ESO-1 is expressed in 100% of myxoid/round cell liposarcoma (MRCL) tumors tested and that MRCL cell lines can be recognized and specifically lysed by NY-ESO-1-specific effectors in vitro. These results establish NY-ESO-1 as an important target antigen for the treatment of patients with MRCL.

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KW - immunotherapy

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KW - sarcoma

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