Clinical Trials Targeting Advanced Cancers by Active Immunization of T-cell Defined Tumor Antigens

Identification of CD8+ and CD4+ T-cell defined tumor antigens has opened the way for possible cancer immunotherapy. Peptide-based active immunization has begun mainly targeting melanoma. Surprisingly, some objective responses were obtained in the initial trials, leading to the accumulation of an explosive number of such antigens. Serological screening of cDNA expression libraries accelerated the identification of immunodominant antigens, resulting in the emergence of the concept of a “cancer-testis antigen.” On the other hand, an advance in basic immunology has been promptly adopted: dendritic cells, as potent professional antigen presenting cells have been preferentially used in combination with the antigen in clinical trials both in vivo and in vitro. Tetramer analysis provided a powerful tool to directly monitor antigen-specific T cells in vivo in these trials. Moreover, adoptive transfer of antigen-specific T cells has added a new perspective to recent cancer immunotherapy.