Recent progress in identification methods for human tumor antigens recognized by T cells

Recent identification of human tumor antigens recognized by T cells made it possible to analyze anti-tumor immune responses quantitatively and qualitatively in human and to develop immunotherapy in a more scientific way. The identification methods have been being improved during the past 10 years. When tumor reactive T-cells are available, DNA expression cloning or direct peptide sequencing from HPLC fractions extracted from MHC class I/peptide complex can be performed. However, it is difficult to establish tumor reactive T cells in many tumors. In those cases, we can apply the reverse immunology approach, in which tumor antigen candidates are first identified by various genetic or immunological methods, including cDNA subtraction between cancers and various tissues with cDNA profiles obtained through systematic gene analysis such as DNA chip/microarrays, SAGE, or public gene databases, or cDNA expression cloning with patients' sera (SEREX). Then antigenicity of the identified candidates is confirmed by demonstration of T cell induction against candidates through in vitro T cell induction or immunization of HLA transgenic mice. We have made various modifications on these techniques. Identification of human tumor antigens in various cancers will lead to development of more effective immunotherapy in the future.