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Generation of a Novel Dendritic-cell Vaccine Using Melanoma and Squamous Cancer Stem Cells
Published on: January 6, 2014
Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library
1Cornell University Medical College, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. ytchen@mail.med.cornell.edu
Abstract:
Cancer/testis (CT) antigens-immunogenic protein antigens that are expressed in testis and a proportion of diverse human cancer types-are promising targets for cancer vaccines. To identify new CT antigens, we constructed an expression cDNA library from a melanoma cell line that expresses a wide range of CT antigens and screened the library with an allogeneic melanoma patient serum known to contain antibodies against two CT antigens, MAGE-1 and NY-ESO-1. cDNA clones isolated from this library identified four CT antigen genes: MAGE-4a, NY-ESO-1, LAGE-1, and CT7. Of these four, only MAGE-4a and NY-ESO-1 proteins had been shown to be immunogenic. LAGE-1 is a member of the NY-ESO-1 gene family, and CT7 is a newly defined gene with partial sequence homology to the MAGE family at its carboxyl terminus. The predicted CT7 protein, however, contains a distinct repetitive sequence at the 5' end and is much larger than MAGE proteins. Our findings document the immunogenicity of LAGE-1 and CT7 and emphasize the power of serological analysis of cDNA expression libraries in identifying new human tumor antigens.
Insights
Researchers identified four cancer/testis (CT) antigen genes, including LAGE-1 and CT7, using melanoma cell expression libraries. This study highlights their potential as targets for novel cancer vaccines.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Cancer/testis (CT) antigens are proteins expressed in normal testis and various human cancers.
- CT antigens are promising targets for developing cancer vaccines due to their immunogenicity.
- Identifying novel CT antigens is crucial for advancing cancer immunotherapy.
Purpose of the Study:
- To discover new cancer/testis (CT) antigens.
- To evaluate the immunogenicity of newly identified CT antigens.
- To demonstrate the utility of serological screening of cDNA expression libraries.
Main Methods:
- Construction of a cDNA expression library from a melanoma cell line.
- Screening the library using patient serum with known antibodies to CT antigens (MAGE-1, NY-ESO-1).
- Isolation and identification of cDNA clones encoding novel CT antigens.
Main Results:
- Four CT antigen genes were identified: MAGE-4a, NY-ESO-1, LAGE-1, and CT7.
- MAGE-4a and NY-ESO-1 were previously known to be immunogenic.
- LAGE-1 and CT7 were identified as newly characterized CT antigens, with CT7 showing distinct structural features.
- The study confirmed the immunogenicity of LAGE-1 and CT7.
Conclusions:
- Serological analysis of cDNA expression libraries is a powerful method for discovering new human tumor antigens.
- LAGE-1 and CT7 represent novel targets for cancer vaccine development.
- The findings expand the repertoire of known CT antigens and their potential therapeutic applications.

