Preclinical evaluation of a class of infectivity-enhanced adenoviral vectors in ovarian cancer gene therapy

Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice

“…Many groups have shown improved infection of CAR-deplete ovarian cancer models using CAR-independent or tropism-modified adenoviral constructs to circumvent the liver and target specific cell types that are normally refractory to adenoviral infection. [32][33][34][35] This could increase the viral load at the tumor site and permit use of lower viral doses, potentially reducing the immune response following virus administration.…”

Transductional targeting of adenovirus vectors for gene therapy

“…92,93 The expanded tropism of this vector has been useful in several other cancer contexts including carcinomas of the ovary, pancreas, colon cancer, and head and neck carcinomas, all of which frequently display highly variable CAR levels. 94 Wu et al 95 demonstrated that Ad vectors with a double fiber modification consisting of a C-terminal poly-lysine stretch, which interacts with heparan sulfates, and the HI-loop RGD provided increased infectivity in several CAR-deficient cell lines, as well as human pancreatic islet cells, 96 ovarian carcinoma 97 and cervical cancer cells in vivo. 98 Other targeting peptides have functioned in the HI-loop locale, including a vascular endothelial cell-binding motif SI-GYLPLP.…”

Advanced Generation Adenoviral Virotherapy Agents Embody Enhanced Potency Based upon CAR-Independent Tropism

“…This CAR deficiency may be explained by the finding that CAR has been shown to exhibit tumor suppression activity (14). Based on this block in viral cell attachment, it has been proposed that gene delivery via CAR-independent pathways may be required to circumvent tumor cell deficiency of CAR (15,16). Thus, it is clear that augmenting infectivity of adenoviral vectors for cancer targets is of fundamental importance to derive their full benefit as adenoviral virotherapy agents.…”