Prognosis of
malignant glioma is poor, and results of treatment remain mediocre. Conditionally replicative adenoviruses hold promise as alternative
anticancer agents for the treatment of
malignant glioma. Here, we evaluated the conditionally replicative adenovirus AdDelta24 and its recently developed derivative AdDelta24-p53, which expresses functional
p53 tumor suppressor protein while replicating in
cancer cells, for treatment of
malignant glioma. In comparison to its parent AdDelta24, AdDelta24-p53 killed most
malignant glioma cell lines and primary
glioblastoma multiforme short-term cultures more effectively, irrespective of their p53 status. Moreover, AdDelta24-p53 caused more frequent regression and more delayed growth of IGRG121 xenografts derived from a
glioblastoma multiforme in vivo. Five intratumoral
injections of 10(7) pfu AdDelta24 gave 24 days median
tumor growth delay (P < 0.01), 30%
tumor regressions, and 30% animals surviving >120 days
tumor-free or with a minimal
tumor residual. The same dose of AdDelta24-p53 caused >113 days of median
tumor growth delay (P < 0.001), 70%
tumor regressions, and 60% animals surviving >120 days
tumor-free or with a minimal
tumor residual. Antitumor effects in vivo were associated with extensive conditionally replicative adenovirus replication, apoptosis induction, and
tumor morphology changes, including dissociation, inflammatory cell infiltration, and
necrosis. We conclude that conditionally replicative adenoviruses expressing p53 are promising new agents for treatment of
malignant glioma.