Cancer Immunity 3:15 (2003) - ARTICLE

The recent identification and molecular characterization of tumor-associated antigens recognized by tumorreactive CD8+ T lymphocytes has led to the development of antigen-specific immunotherapy of cancer. Among other approaches, clinical studies have been initiated to assess the in vivo immunogenicity of tumor antigenderived peptides in cancer patients. In this study, we have analyzed the CD8+ T cell response of an ocular melanoma patient to a vaccine composed of four different tumor antigen-derived peptides administered simultaneously in incomplete Freund's adjuvant (IFA). Peptide NY-ESO-1157-165 was remarkably immunogenic and induced a CD8+ T cell response detectable ex vivo at an early time point of the vaccination protocol. A CD8+ T cell response to the peptide analog Melan-A26-35 A27L was also detectable ex vivo at a later time point, whereas CD8+ T cells specific for peptide tyrosinase368-376 were detected only after in vitro peptide stimulation. No detectable CD8+ T cell response to peptide gp100457-466 was observed. Vaccine-induced CD8+ T cell responses declined rapidly after the initial response but increased again after further peptide injections. In addition, tumor antigen-specific CD8+ T cells were isolated from a vaccine injection site biopsy sample. Importantly, vaccine-induced CD8+ T cells specifically lysed tumor cells expressing the corresponding antigen. Together, these data demonstrate that simultaneous immunization with multiple tumor antigen-derived peptides can result in the elicitation of multiepitope-directed CD8+ T cell responses that are reactive against antigenexpressing tumors and able to infiltrate antigen-containing peripheral sites. http://www.cancerimmunity.org/v3p15/030915.htm (1 of 14) Cancer Immunity 3:15 (2003) ARTICLE