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Published on: May 12, 2023
NY-ESO-1 is a ubiquitous immunotherapeutic target antigen for patients with myxoid/round cell liposarcoma
Seth M Pollack1, Achim A Jungbluth, Benjamin L Hoch
1Fred Hutchinson Cancer Research Center, Seattle, WA, USA. spollack@fhcrc.org
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.
Insights
Myxoid/round cell liposarcoma (MRCL) frequently expresses the NY-ESO-1 antigen, making it a promising target for new therapies. This study confirms NY-ESO-1 as a viable target for MRCL treatment.
Area of Science:
- Oncology
- Immunology
- Sarcoma Research
Background:
- Myxoid/round cell liposarcoma (MRCL) is a common soft tissue sarcoma subtype with poor outcomes in metastatic disease.
- NY-ESO-1 is a cancer-testis antigen successfully targeted in various cancer therapies.
Purpose of the Study:
- To evaluate the prevalence and expression levels of NY-ESO-1 in MRCL tumors.
- To assess the potential of NY-ESO-1 as a therapeutic target in MRCL.
Main Methods:
- Immunohistochemistry and quantitative reverse transcriptase-polymerase chain reaction were used to analyze NY-ESO-1 expression in 25 MRCL tumor samples.
- In vitro chromium release assays were performed to evaluate NY-ESO-1-specific T-cell recognition and lysis of MRCL cell lines.
Main Results:
- NY-ESO-1 expression was detected in 100% of assessed MRCL tumors, with homogeneous and robust staining in most cases (72%).
- The majority of tumors showed sufficient NY-ESO-1 expression (2+) for patient eligibility in clinical trials.
- In vitro studies demonstrated the sensitivity of MRCL cell lines to lysis by NY-ESO-1-specific CD8-positive T-cells.
Conclusions:
- NY-ESO-1 is highly prevalent and consistently expressed in MRCL tumors.
- These findings establish NY-ESO-1 as a significant and actionable therapeutic target for MRCL patients.
