A RECOMBINANT ADENOVIRAL VECTOR EXPRESSING FULL-LENGTH HUMAN RETINOBLASTOMA SUSCEPTIBILITY GENE INHIBITS HUMAN TUMOR-CELL GROWTH

As a prelude to considering retinoblastoma (RB) gene therapy for cance r, a series of human tumor cell lines with either full-length, mutated , or undetectable RB protein were treated with recombinant adenovirus encoding RB (ACNRB). Both RB protein expression and the cytotoxic and antiproliferative effects of ACNRB treatment were evaluated. While the transgene expression of a reporter virus encoding the beta-galactosid ase enzyme (rAd-beta-gal) varied among cell lines, the reintroduction and expression of the RE gene resulted in a pronounced inhibition of c ellular proliferation in RB-altered cell lines. An antiproliferative r esponse was observed with control adenovirus treatment in some cell li nes. ACNRB treatment did not cause detectable cytotoxicity in either R B+ or RB-altered cells. Dose-dependent cytostasis was observed in RB- cell lines. In vivo tumor suppression was observed in a breast xenogra ft model subsequent to the treatment of established tumors with ACNRB. These data support a role for RE gene therapy of tumors with RE mutat ions and provide a basis for the further evaluation of ACNRB gene ther apy of human cancer.