Cancer-testis antigen expression in canine melanoma and healthy tissues

Abstract

Cancer-testis antigens (CTAs) are promising targets for immuno-oncotherapy. They offer the potential to treat cancers for which effective systemic therapies are lacking, including canine malignant melanoma (CMM). In this study, we investigate the suitability of eight canine orthologs of human CTAs as targets for immunotherapy, including cancer-associated gene 1 (CAGE1), CCCTC-binding factor (CTCFL), DEAD-box helicase 53 (DDX53), the melanoma antigen gene (MAGE), 5'-nucleotidase, cytosolic IB (NT5C1B), P antigen family member 3-like (PAGE3-like), preferentially expressed antigen in melanoma (PRAME), and synovial sarcoma X chromosome breakpoint (SSX). MAGE proteins were detected by immunohistochemistry in 12.1 % (4/33) of CMM cases, including digital and oral melanoma, with healthy tissue expression restricted to the testis. CTA mRNA was detected by Real-time PCR in canine testis and validated through gel electrophoresis and Sanger sequencing. MAGE, PAGE3-like, and PRAME mRNA were strongly expressed in canine oral melanoma and metastatic cell lines with restricted expression in normal tissues. CAGE1, CTCFL, DDX53, and SSX6 were only weakly expressed or absent in canine oral melanoma. CTCFL and DDX53 expression in healthy tissues was not restricted to the testis, as moderate expression was found in the kidney. These results suggest that dogs express CTAs, similar to humans, and thus CTAs may serve as a target for immunotherapy in dogs.

Keywords: Cancer-testis antigens; Canine melanoma; Canine oral melanoma; Immunohistochemistry; Immunotherapy; RT-PCR.