Nuclear delivery of p53 C-terminal peptides into cancer cells using scFv fragments of a monoclonal antibody that penetrates living cells.

scFv fragments of a monoclonal antibody that penetrates living cells and localizes in nuclei were designed as fusion proteins with C-terminal p53 peptides and tested for restoring p53 function in p53 mutant cancer cells. scFv fragments transported a 30-mer C-terminal peptide of p53 into cancer cells and induced cellular cytotoxicity in contrast to scFv fragments alone and other scFv-p53 fusion peptides. Cellular toxicity was not observed with scFv fragments containing a single mutation in VH that prevented antibody penetration. Our results demonstrate the potential efficacy of antibody scFv fragments as a nuclear delivery system in cancer cells.