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

• Published in: Cancer 2012-09, Vol.118 (18), p.4564-4570
• Main Authors: 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, III, Ernest U., Jones, Robin L., Yee, Cassian
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm - analysis; Antigens, Neoplasm - immunology; Biological and medical sciences; cancer testis antigens; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Dermatology; Humans; Immunohistochemistry; Immunotherapy; Liposarcoma, Myxoid - immunology; Liposarcoma, Myxoid - therapy; Medical sciences; Membrane Proteins - analysis; Membrane Proteins - immunology; myxoid; NY‐ESO‐1; Reverse Transcriptase Polymerase Chain Reaction; sarcoma; Tumors; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.27446

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.