Identification of the gonad-specific anion transporter SLCO6A1 as a cancer/testis (CT) antigen expressed in human lung cancer.
Serological analysis of recombinant cDNA expression libraries (SEREX) has led to the identification of many of the antigens recognized by the immune system of cancer patients, which are collectively referred to as the cancer immunome. We used SEREX to screen a testicular cDNA expression library with sera obtained from non-small cell lung cancer patients and isolated cDNA clones for 82 antigens. These included a total of 31 antigens previously identified by SEREX, and 51 that did not match entries in the Cancer Immunome Database and were considered newly identified antigens. Overall, the antigens comprised 62 known proteins and 20 uncharacterized gene products. Six antigens (NY-TLU-6, -37, -39, -57, -70, -75) were identified as putative cell surface proteins that are potential targets for monoclonal antibody-based immunotherapy. Of these, the gonad-specific anion transport protein SLCO6A1 (NY-TLU-57) was shown to be tissue-restricted. RT-PCR showed it to be expressed strongly only in normal testis, and weakly in spleen, brain, fetal brain, and placenta. In addition, NY-TLU-57 mRNA was found in lung tumor samples (5/10) and lung cancer cell lines (6/11), as well as bladder (5/12) and esophageal (5/12) tumor samples. These data suggest that SLCO6A1 is a putative cancer/testis (CT) cell surface antigen of potential utility as a target for antibody-based therapy for a variety of tumor types. The analysis also permits us to estimate the eventual size of the SEREX-defined cancer immunome at around 4000 genes. This emphasizes the importance of continued SEREX screening to define the cancer immunome.
Lee
Sang-Yull
SY
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Williamson
Barbara
B
Caballero
Otavia L
OL
Chen
Yao-Tseng
YT
Scanlan
Matthew J
MJ
Ritter
Gerd
G
Jongeneel
C Victor
CV
Simpson
Andrew J G
AJ
Old
Lloyd J
LJ
D027321:Anion Transport Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics / Q000276:immunology*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D015723:Gene Library; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008297:Male; D027361:Organic Anion Transporters / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013737:Testis / Q000276:immunology
D027321:Anion Transport Proteins; D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C487009:SLCO6A1 protein, human