A novel triple-regulated oncolytic adenovirus carrying p53 gene exerts potent antitumor efficacy on common human solid cancers

Abstract

Conditionally replicating adenoviruses (CRAd) can replicate specifically in cancer cells and lyse them. The CRAds were widely used in the preclinical and clinical studies of cancer therapy. We hypothesize that more precisely regulated replication of CRAds may further improve the vector safety profile and enhance its antitumor efficacy.

A Novel E1B-55kD-Deleted Oncolytic Adenovirus Carrying Mutant KRAS-Regulated hdm2 Transgene Exerts Specific Antitumor Efficacy on Colorectal Cancer Cells

“…Paradoxically, enhanced p53 expression increased the oncolytic potency of CRAds in the presence of E1B-55kD (30,31). The dilemma can be explained by two phenomena.…”

Anticancer Gene Transfer for Cancer Gene Therapy

“…One example of an effective oncolytic armed with a tumor suppressor is the generation of an oncolytic adenovirus with E1A under the hTERT and hypoxia response element promoter and the TP53 gene under a cytomegalovirus promoter. This virus combined tumor selectivity, p53 tumor suppressor expression and oncolysis (Wang et al, 2008). Cancer is a multifactorial disease and many signaling pathways are altered during its initiation and progression.…”

Adenovirus-Based Gene Therapy for Cancer

“…All mice died at a high dosage of wAd5, and the therapeutic dosage induced an obvious increase of liver enzymes and evidence of cytopathic effects on liver tissues. Therefore, the toxic effect of hTERT promoter-regulated CRAds is much weakened compared with wAd5 by the use of the hTERT promoter (Su et al, 2004(Su et al, , 2006b(Su et al, , 2008aWang et al, 2008).…”

“…It brings us a rekindled hope for overcoming the genetic diseases including cancer. Adenoviral vectors have been used extensively in cancer gene therapy (Su et al, 2008;Yang et al, 2007). Most of them are replication-deficient (Yang, 1995).…”