| abstract |
Mutations to the tumor suppressor protein p53 have been observed in 40-60% of all human cancers. These mutations are often accompanied by high nuclear and cytoplasmic concentrations of p53. Because many tumors show very high p53 levels, this protein is an attractive target for cancer immunotherapy. Unfortunately, p53 is a self-antigen that is likely to be tolerated as a self-protein by the immune system. The present invention is based on the discovery that this self-tolerance is overcome by administration of recombinant, modified, vaccinia, ankara (MVA) containing a nucleic acid encoding p53 (rMVAp53). The present invention discloses a method for generating a p53-specific CTL response against tumor cells expressing mutant p53 by administration of a composition comprising rMVAp53. Administration of rMVAp53 reduces tumor development, tumor growth, and mortality in various malignant cell types. These effects are enhanced by the administration of CTLA-4 blockers and / or CpG oligodeoxynucleotide immunomodulators. |