Preclinical Characterization of the Antiglioma Activity of a Tropism-Enhanced Adenovirus Targeted to the Retinoblastoma Pathway

Abstract

The antitumor activity of Delta-24-RGD suggests that it has the potential to be an effective agent in the treatment of gliomas.

Expression of the coxsackievirus- and adenovirus receptor in gastrointestinal cancer correlates with tumor differentiation

“…An example of such virus is the Delta-24-arginineglycine-aspartate (RGD)-adenovirus, which has been engineered to express RGD sequences in the knob protein, resulting in preferred binding to integrins. 29 Clinical trials with this virus are planned.…”

Gene Therapy Progress and Prospects: cancer gene therapy using tumour suppressor genes

“…32 D24-RGD is capable of lysing ovarian carcinoma and glioma cells in vitro, as well as extending the survival of mice-bearing xenografts of both tumour types. 32,33 Of note, D24-RGD appeared to have a significantly greater cytopathic effect than D24 and its replication on normal human astrocytes was at least 3 log scales lower than a wild-type adenovirus. 33 Clinical trials of both D24-RGD and dl922/947 are imminent.…”

“…32,33 Of note, D24-RGD appeared to have a significantly greater cytopathic effect than D24 and its replication on normal human astrocytes was at least 3 log scales lower than a wild-type adenovirus. 33 Clinical trials of both D24-RGD and dl922/947 are imminent. Further adenoviral mutants also explore targeting of the Rb pathway.…”

Viruses, gene therapy and stem cells for the treatment of human glioma

“…32 The paucity of Coxsackie adenovirus receptors on tumor cells led to the construction of the Delta-24-RGD, that has an RGD-4C peptide motif inserted into the adenoviral fiber, which allows the adenovirus to anchor directly to integrins. 33 Delta-24-RGD administered in four glioblastoma stem cell lines and xenografts derived from glioma stem cells showed induction of tumor cell death by autophagy both in vitro and in vivo. 34 ICOVIR-5 adenovirus encompasses an early 1A adenoviral (E1A) deletion in the retinoblastoma (Rb) protein-binding region, substitution of the E1A promoter for E2F-responsive elements and an RGD-4C peptide motif inserted into the adenoviral fiber to enhance adenoviral tropism.…”