Ras and p53 intracellular targeting with recombinant single-chain Fv (scFv) fragments: A novel approach for cancer therapy?

Intracellular expression of recombinant antibodies allows one to interfere with the functions of oncogenic molecules expressed in various cell compart ments and has therefore a vast clinical potential in cancer therapy. We inh ibited the functions of oncogenic Ras mutant forms by intracellular express ion of a neutralizing single-chain antibody (scFv). In vitro studies indica ted that the scFv is expressed in the cytosol of Xenopus laevis oocytes and of tumor cells, blocks ms-mediated activation processes, and induces tumor cell death. In vivo studies performed using scFv cDNA inserted into an ade noviral vector showed that the scFv dramatically affects tumor growth. Seco nd, intracellular expression of scFvs directed against p53 indicated that t hese antibody fragments can be successfully targeted to cell nucleus, bind p53, and partially restore the transcriptional activity of p53 mutants in h uman tumor cells. Thus, intracellular scFvs directed against oncogenic mole cules may represent a new class of antitumor agents.