Abstract
A new era of cancer immunotherapy has arrived and is based on the molecular identification of human cancer antigen. Several antigen peptide epitopes recognized by human CD8+ cytotoxic T-lymphocyte (CTL) clones reactive with human cancer target cells have been reported. An analysis of CTLs reactive with melanoma cells has identified several different categories of antigen peptides. A wild-type proto-oncogene HER2 is expressed at high levels in a variety of human cancers, such as ovarian, breast, and nonsmall cell lung cancer. We established a CTL clone directed against a HER2-derived peptide from a HLA-A2402-positive healthy individual and a CTL clone lysed HER2-expressing cancer cell line with HLA-A2402 restriction. Vaccination with these peptides is now in an early phase of clinical trial. Antileukemia immunotherapy has been extensively investigated and clinically practiced. However, few tumor antigens that could be specifically recognized by CTL have been identified in leukemia. Some candidates such as PRAME, proteinase 3, WT1, and hTERT might be useful and applicable for the treatment of hematological malignancy. On the basis of reliable preclinical data, new immunotherapy protocols will need to be evaluated clinically. Careful monitoring of immune responses and side effects will soon ensure the identification of effective immunotherapy protocols for human malignancies.
