Dendritic Cell Immunization Induces Nonprotective WT1-specific CTL Responses in Mouse

Abstract

In the present article we describe the immunogenicity in the mouse of 2 epitopes from the tumor-associated antigen Wilms tumor 1 antigen (WT1). The newly described K-restricted pWT330 epitope stimulates high-avidity allo-major histocompatibility complex restricted cytotoxic T lymphocyte (CTL) capable of killing WT1-expressing tumor cell lines. The epitope pWT126 has been previously described as a D-restricted CTL epitope. Both epitopes are weakly immunogenic as immunization with incomplete Freund adjuvant induced poor CTL responses. In contrast, when coated onto dendritic cells (DCs) both peptides readily induced CTL responses. However, these peptide-specific CTL were of low avidity and unable to recognize WT1-expressing tumor cells in vitro and to protect against tumor challenge in vivo. In contrast, vaccination with DCs coated with peptides derived from the nonself antigen ovalbumin (OVA) induced CTL that recognized OVA-expressing tumor cells and protected against tumor growth in vivo. These data show that although DC vaccination readily stimulated CTL against WT1 peptides, these CTL did not display antitumor activity in vitro and in vivo. This suggests that tolerance to the 2 WT1 epitopes interferes with the generation of protective CTL immunity in mice.