P53 AS A TARGET FOR CANCER VACCINES - RECOMBINANT CANARYPOX VIRUS VECTORS EXPRESSING P53 PROTECT MICE AGAINST LETHAL TUMOR-CELL CHALLENGE

The p53 protein is an attractive target for immunotherapy, because mut ations in the p53 gene are the most common genetic alterations found i n human tumors. These mutations result in high levels of p53 protein i n the tumor cell, whereas the expression level of wild-type p53 in non malignant tissue is usually much lower. Several canarypox virus recomb inants expressing human or murine p53 in wild-type or mutant form were constructed, Immunization with these viruses protected BALB/c mice fr om a challenge with an isogenic and highly tumorigenic mouse fibroblas t tumor cell line expressing high levels of mutant p53. The tumor prot ection was equally effective regardless of whether wild-type or mutant p53 was used for the immunization, indicating that the immunologic re sponse was not dependent on any particular p53 mutation and that immun ization with this live virus vaccine works effectively against mutant p53 protein expressed in a tumor cell. In tumors escaping immunologic rejection, the expression of the p53 protein was commonly down-regulat ed.