Enhancement of Efficacy of Wilms’ Tumor Gene WT1 Product-derived Peptide Cancer Vaccine by Co-administration with Immunopotentiating Agents: Lessons from Mouse Models

Abstract

To induce and activate tumor-associated antigen-specific cytotoxic T lymphocytes (CTLs) for cancer immunity, it is important not only to select potent CTL epitopes but also to combine them with appropriate immunopotentiating agents. Wilms’ tumor gene W T1 is expressed at high levels in many kinds of hematological and solid malignancies. WT1 gene products have high immunogenicity and have been reported to serve as a promising cancer antigen for tumor-specific immunotherapy. We have started WT1 peptide vaccine clinical trials since 2001, and demonstrated that WT1 peptide can induce WT1-specific immunologic responses and the associated clinical responses. To enhance the WT1 peptide vaccine’s therapeutic efficacy, we investigated various immunopotentiating agents that co-administer with WT1 peptide vaccine, using mice models for WT1 peptide cancer immunotherapy. Mycobacterium bovis bacillus Calmette-Guerin cell wall skeleton (BCG-CWS), which is well-known to activate dendritic cells (DCs), i.e., activate innate immunity, could induce and/or activate WT1-specific CTLs in combination with WT1 peptide vaccination. Interferon (IFN)-β is a type I IFN, and is known for its various anticancer properties. Co-administration of WT1 peptide and IFN-β enhanced tumor immunity mainly through the induction of WT1-specific CTLs, enhancement of natural killer (NK) activity, and promotion of major histocompatibility complex (MHC) class I expression on the tumor cells. WT1 peptide vaccination combined with BCG-CWS or IFN-β can thus be expected to enhance the clinical efficacy of WT1 immunotherapy.