Cancer/testis (CT) antigens are a category of tumor antigens with normal expression restricted to adult male germ cells in the testis. Melanoma antigen A1 (MAGE-A1) was the first identified CT antigen. The discovery that MAGE-A1 was found to be expressed in various types of cancer made it an attractive candidate for a cancer vaccine. However, result from clinical trial attempting to eliminate tumor cells in patients was not satisfactory. In this study we look for alternative method of improving the immunogenicity of MAGE-A1. Previous studies have shown that using xenogenic homologous proteins can enhance immune responses towards cancer. In this study, we employ the idea of using homologous protein to enhance immune responses towards hepatocellular carcinoma. The mouse Mage-a1 homolog (s...[ Read more ]

Cancer/testis (CT) antigens are a category of tumor antigens with normal expression restricted to adult male germ cells in the testis. Melanoma antigen A1 (MAGE-A1) was the first identified CT antigen. The discovery that MAGE-A1 was found to be expressed in various types of cancer made it an attractive candidate for a cancer vaccine. However, result from clinical trial attempting to eliminate tumor cells in patients was not satisfactory. In this study we look for alternative method of improving the immunogenicity of MAGE-A1. Previous studies have shown that using xenogenic homologous proteins can enhance immune responses towards cancer. In this study, we employ the idea of using homologous protein to enhance immune responses towards hepatocellular carcinoma. The mouse Mage-a1 homolog (sharing 60% protein sequence similarity with human MAGE-A1) was used to compare with human MAGE-A1 as a target protein to stimulate immune responses. Dendritic cells pulsed with bacterial expressed human MAGE-A1 and mouse Mage-a1 proteins were used to prime CD8+ T cells. Effects of the CD8+ T cells against cancer cells were evaluated by quantifying the amount of interferon-γ secreted in ELISPOT assay and measuring the cytotoxic effect of CD8+ T cells in LDH-releasing cytotoxicity assay. The results showed that the mouse Mage-a1-specific CD8+ T cells are able to respond to the MAGE-A1⁺ human cancer cells and the response elicited is antigen specific and HLA-class I restricted. I therefore present the mouse Mage-a1 as a potential cancer vaccine candidate for generating anti-tumor response in vitro.