Anti‐tumor efficacy of a transcriptional replication‐competent adenovirus, Ad‐OC‐E1a, for osteosarcoma pulmonary metastasis

Abstract

These data demonstrated that OC promoter could direct adenovirus replication by controlling the E1a gene to target human OSPM in a tumor-specific manner, providing an efficient tool to develop a feasible therapeutic modality for OSPM.

Prostate-Restricted Replicative Adenovirus Expressing Human Endostatin-Angiostatin Fusion Gene Exhibiting Dramatic Antitumor Efficacy

“…Adenovirus-mediated gene therapy has been tested broadly in clinical trials, and tumor/tissue-restricted replicative adenovirus showed significant advantages over replication-deficient adenovirus (14,28,29). However, the single administration of PRRA ultimately results in failure due to inefficient viral distribution in tumor masses (12,14).…”

Evolving gene therapy approaches for osteosarcoma using viral vectors: Review

“…Recently in this model the CRAd Ad-OC-E1a construct was evaluated and showed a significant decrease in tumor nodules. Moreover, normal lung tissue was not affected when using this intravenous administrated vector (84). In addition, the canine model developed by us (59) should be a valuable model to study delivery in an immune-competent context as canine OS bears a striking resemblance to human OS and thus will be a useful model for testing gene therapy approaches.…”

Viral-based gene delivery and regulated gene expression for targeted cancer therapy

“…In addition, the promoter of the CREBBP/EP300 inhibitory protein 1 (CRI1), a gene specifically expressed in malignant pleural mesothelioma, was used to drive E1a-mediated virotherapy that specifically kills malignant mesothelioma cells but not normal cells [83]. Other tumor-specific promoters used to drive E1-mediated virotherapy against various cancers include mucin-1 promoter [84], osteocalcin promoter [85], AFP promoter [55], midkine promoter [86] and COX-2 promoter [87,88]. In general, regulation of therapeutic transgene expression (such as E1a) by a tumor-specific promoter is preferred over tissue-specific promoter strategy for several reasons: i) not all tissue-specific promoters are available for every organ/tissue; ii) only a few of organs/ tissues are dispensable, such as the prostate, while most serve critical life-sustaining functions; and iii) tumorspecific promoters that express only in cancer cells, not (or express at a much lower level) in normal cells, such as telomerase and survivin, provide an ideal tumor targeting with minimal toxicity and maximal anticancer effect.…”