Gene transfer techniques may provide efficient treatment for a variety of malignant neoplasms. A replication-deficient adenovirus (Ad) vector which carries the cDNA for wild-type p53 (AdCMV.p53) was tested for its in vitro and in vivo effects on the growth of murine melanoma cell and prostatic cancer cells. Cells infected with AdCMV.p53 were growth inhibited. DNA laddering using agarose gel electrophoresis and in situ labeling of DNA fragmentation (TUNEL) showed that AdCMV.p53-infected cancer cells underwent apoptosis. Nude mice injected subcutaneously with melanoma cells developed localized tumors. These tumors were subsequently infiltrated either with AdCMV.p53, with AdCMV.NLSagal (2x109 pfu), or with saline alone. One week after infection melanomas exposed to AdCMV.p53 were significantly smaller than control tumors. A similar result was observed with prostatic cancer cells infected ex vivo and subsequently injected subcutaneously in mice. Therefore, Ad-mediated wild-type p53 overexpression resulted in melanoma and prostatic cancer cell apoptosis in vitro and inhibition of tumor growth in vivo. These gene therapy approaches may be useful in targeting melanoma and prostatic tumors in a clinical setting. A preliminary study has been performed to determine whether intravenous basic fibroblast growth factor (bFGF) protects, against bone marrow hypoplasia following radiation therapy. The results show that in C3H mice bFGF enhanced LD50 at 30 days in a dose-dependent fashion. Additional experiments will examine in a similar animal model the therapeutic potential of an Ad vector which carries the cDNA for bFGF. In summary, gene therapy with Ad vectors may provide a novel approach to induce programmed cell death of cancer cells. In addition, gene transfer of bFGF may enhance the resistance of bone marrow cells to radiation therapy. The biosafety and clinical applicability of the above approaches will be examined in future studies.
