REPLICATION OF ONYX-015, A POTENTIAL ANTICANCER ADENOVIRUS, IS INDEPENDENT OF P53 STATUS IN TUMOR-CELLS

The 55-kDa E1B protein of adenovirus, which binds to and inactivates t he tumor suppressor protein p53, is not expressed in the adenoviral mu tant termed ONYX-015 (i.e., dl1520). It was reported that the mutant v irus due to a deletion in E1B is able to replicate only in cells defic ient for wild-type p53, Accordingly, dl1520 is currently being evaluat ed as a potential tool in the therapy of p53 deficient cancers. In con trast, we report here that dl1520 replicates independently of the p53 status in various tumor cell lines (U87, RKO, A549, H1299, and U373), In addition, the inhibition of p53-mediated transcriptional activation in wild-type p53 containing U2OS cells, by overexpression bf a transd ominant negative p53 mutant, did not render the cells permissive for d l1520 replication. Finally, we show that, depending on the multiplicit y of infection, the deleted virus is able to replicate in and to kill primary human cells. Thus, the molecular basis for the growth differen ces of dl1520 within different cell types remains to be determined.