Cancer Immunity 4:13 (2004)

Identification of the gonad-specific anion transporter SLCO6A1 as a cancer/testis (CT) antigen expressed in human lung cancer

Sang-Yull Lee^1*, Barbara Williamson¹, Otavia L. Caballero², Yao-Tseng Chen³, Matthew J. Scanlan^1**, Gerd Ritter¹, C. Victor Jongeneel⁴, Andrew J. G. Simpson¹, and Lloyd J. Old¹

¹Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
²Ludwig Institute for Cancer Research, Sao Paulo Branch, Rua Professor Antonio Prudente 109-4 andar, Liberdade 01509-010, Sao Paulo, SP, Brazil
³Department of Pathology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
⁴Office of Information Technology, Ludwig Institute for Cancer Research, and Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland
^*Present address: Department of Biochemistry, College of Medicine, Pusan National University, 1Ga 10, Ami-dong, Seo-gu, Busan 602-739, Korea
^**Deceased

Keywords: human, SEREX, cancer/testis, tumor antigens, SLCO6A1, mRNA, tissue distribution

Abstract

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.