Characterization of mutant ß-Catenin as a target molecule for antigen-specific immunotherapy in Wilms tumors

Tumor cells are different from normal cells in that they express a unique set of proteins which are derived from the expression of mutated onco- and tumor suppressor genes – an invaluable source of candidate antigens for the development of targeted cancer immunotherapy. Several findings suggest that mutant ß-catenin may represent an attractive target-antigen for the development of cancer immunotherapy in Wilms tumors (WTs). Mutations of the ß-catenin proto-oncogene are causatively involved in a significant proportion of WTs. The majority of ß-catenin mutations in WTs are confined to a single codon (Ser45) providing a common target in different patients. Finally, mutant ß-catenin has already been identified as a bona fide tumor-associated antigen in melanoma patients that can be selectively recognized by tumor-infiltrating T-lymphocytes, thereby providing unambiguous evidence for ß-catenin's potential immunogenicity in humans. As a first step towards an antigen-specific cancer vaccine we have developed a B-cell targeting approach in combination with a potent cholera-toxin based vaccine adjuvant to efficiently deliver soluble antigens to antigen-presenting B-cells in vivo.