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A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening
Y T Chen1, M J Scanlan, U Sahin
1Cornell University Medical College, New York, NY 10021, USA.
Abstract:
Serological analysis of recombinant cDNA expression libraries (SEREX) using tumor mRNA and autologous patient serum provides a powerful approach to identify immunogenic tumor antigens. We have applied this methodology to a case of esophageal squamous cell carcinoma and identified several candidate tumor targets. One of these, NY-ESO-1, showed restricted mRNA expression in normal tissues, with high-level mRNA expression found only in testis and ovary tissues. Reverse transcription-PCR analysis showed NY-ESO-1 mRNA expression in a variable proportion of a wide array of human cancers, including melanoma, breast cancer, bladder cancer, prostate cancer, and hepatocellular carcinoma. NY-ESO-1 encodes a putative protein of Mr 17,995 having no homology with any known protein. The pattern of NY-ESO-1 expression indicates that it belongs to an expanding family of immunogenic testicular antigens that are aberrantly expressed in human cancers in a lineage-nonspecific fashion. These antigens, initially detected by either cytotoxic T cells (MAGE, BAGE, GAGE-1) or antibodies [HOM-MEL-40(SSX2), NY-ESO-1], represent a pool of antigenic targets for cancer vaccination.
Insights
Researchers identified NY-ESO-1, a novel tumor antigen, using Serological analysis of recombinant cDNA expression libraries (SEREX). This antigen is expressed in various cancers and represents a potential target for cancer vaccination.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Serological analysis of recombinant cDNA expression libraries (SEREX) is a method to identify tumor antigens.
- Tumor antigens are proteins that elicit an immune response against cancer cells.
Purpose of the Study:
- To identify immunogenic tumor antigens in esophageal squamous cell carcinoma.
- To characterize the expression pattern of a novel antigen, NY-ESO-1.
Main Methods:
- SEREX was performed using tumor mRNA and autologous patient serum.
- Reverse transcription-PCR (RT-PCR) was used to analyze NY-ESO-1 mRNA expression in various cancer types and normal tissues.
Main Results:
- NY-ESO-1 was identified as a candidate tumor antigen.
- NY-ESO-1 mRNA was highly expressed in testis and ovary but restricted in other normal tissues.
- NY-ESO-1 mRNA was detected in a variable proportion of melanoma, breast, bladder, prostate, and hepatocellular carcinomas.
- NY-ESO-1 encodes a novel protein with no homology to known proteins.
Conclusions:
- NY-ESO-1 belongs to a family of immunogenic testicular antigens aberrantly expressed in cancers.
- NY-ESO-1 is a potential antigenic target for cancer vaccination strategies.