ABSTRACT The existence of anti-tumor immune system has been reported and was proved by many experiments. A lot of tumor specific antigens as a target of immune system were identified and some have been applied for cancer vaccine. Since NY-ESO-1, one of cancer-testis antigens, was reported to be expressed frequently in cancers and to possess strong immunogenicity, it is also used for worldwide cancer vaccine trials. We have performed a cancer vaccine clinical trial with NY-ESO-1 protein and observed NY-ESO -1 specific immune responses in most of patients vaccinated. Some patients showed preferable clinical responses. Cancer vaccine was developed rapidly in the last decade, however there still left several problems to be resolved for the spread of cancer vaccine.